1,721,004 research outputs found
Mechanisms of optimised plasticity: training associated enhancement of transplant-mediated brain repair in a rodent model of Huntington’s disease
No full textThis thesis dealt with the subject of neurorehabilitation via cell replacement therapy in the neurodegenerative disease of Chorea Huntington in the rodent model.Cell-based treatment of neurodegenerative diseases has been tested clinically with partial success. A feature of the clinical studies has been to focus on the cell preparation and technical issues prior to the transplantation without presupposing that the outcome of the therapy might be influenced by events after the surgery. Similarly, basic research, almost entirely empirical, supports the hypothesis that - under certain conditions - cell therapy can reverse some functional deficits. However, there is limited understanding of the biological rationale behind the recovery as this aspect has been considered secondary.This medical thesis aimed to address this issue of brain recovery. To optimize graft-mediated benefits an improved understanding of substrates and mechanisms underlying graft plasticity, and factors impacting on plasticity, is fundamental. Using primary grafts in rodent models of Huntington’s disease (HD) identification and analyzation of morphological, cellular and molecular changes in grafts associated with plasticity is performed. The hypothesis tested will be to study whether grafts can be manipulated by different schedules and intensities.70 animals were trained with the paw reaching test categorized in specific (SP) and nonspecific (NSP) groups, followed by a striatal quinolinic acid (QA) lesion and afterwards transplanted with embryonic stem cells resulting in a transplant (TX), lesion (LX) and control (CO) group.Behavioural testing, histological evaluation and molecular downstream analysis focusing on plasticity genes is performed to analyze if specific training modalities have the potential to make an expedient contribution to neuronal plasticity and recovery in a rodent model of HD.The obtained data could show that specific training improves motoric skills in transplanted animals and the individually trained rodent’s express plasticity markers within the transplant in a higher level than untrained animals
Exofokale postischämische Degeneration dopaminerger Neurone am Tiermodell eines photothrombotischen Schlaganfalls
No full textDiversity of GABAergic interneurons in the dentate gyrus of the transgenic GAD67-eGFP([delta]neo)-knock-in-mouse line
No full textInterneurone bilden eine extrem heterogene Population, die eine differenzierte inhibitorische Kontrolle von Erregungsbildung und Erregungsfluss in cortikalen Schaltkreisen ermöglicht. In dieser Arbeit wurde eine Charakterisierung der Interneurone des Gyrus dentatus durchgeführt, der als Eingangsstruktur in den hippocampalen Schaltkreis eine strategisch wichtige Position einnimmt. Zur unvoreingenommenen intraexperimentellen Zellselektion wurde die GAD67-eGFP-knock-in Mauslinie, bei der abhängig von der Expression der GABA-synthetisierenden Enzymisoform GAD67 das Fluoreszenzprotein eGFP gebildet wird, zuerst immunhistochemisch validiert und dann als Modellsystem verwendet.
Bei 105 der eGFP-markierten Interneurone wurden mithilfe der Patch-Clamp-Technik die Morphologie sowie passive und aktive elektrophysiologische Membraneigenschaften bestimmt. Bei 19 Interneuronen wurde zudem eine dreidimensionale Neurolucida-Rekonstruktion durchgeführt. Die lichtmikroskopische Analyse sowie eine auf den quantitativen Daten der rekonstruierten Neurone basierende hierarchische Clusteranalyse
ergab eine morphologische Einteilung in fünf Klassen: BC-Zellen (Axon in der Körnerzellschicht), HICAP-Zellen (Axon in der inneren Molekularschicht), HIPP-Zellen (Axon in der mittleren und äusseren Molekularschicht), TML-Zellen (Axon in der gesamten Molekularschicht) und ML-Zellen (Soma und Axon in der Molekularschicht). Diese Einteilung ist vor allem durch die Schichtspezifität der Axonprojektion gekennzeichnet und weist auf eine differenzierte Regulation der unterschiedlichen Prinzipalzellkompartimente (Soma vs. Dendriten) sowie der Eingangstrakte (Tractus perforans und associativus) des Gyrus dentatus hin.
Bei der Analyse der elektrophysiologischen Eigenschaften der identifizierten Interneuronklassen fielen charakteristische Aktionspotentialmuster sowie zahlreiche statistisch signifikante Unterschiede in den passiven und aktiven Membraneigenschaften zwischen den Klassen auf. Eine auf den physiologischen Charakteristika von 65 identifizierten Zellen basierende hierarchische lusteranalyse ergab eine Unterteilung, die der morphologischen Klassifizierung im Wesentlichen entsprach. Daraus folgt, dass Interneurone des Gyrus dentatus in fünf distinkte, durch ihre Morphologie und ihre Physiologie gekennzeichnete Typen unterteilt werden können. Diese könnten unterschiedliche funktionelle Aufgaben im Schaltkreis des Gyrus dentatus wie z.B. die Synchronisation von Prinzipalzellensembles oder die Kontrolle synaptischer Eingänge an den Prinzipalzelldendriten übernehmen.Interneurons build an extremely heterogeneous population performing a differentiated control of excitability and information flow in cortical circuits. Here, the interneurons of the dentate gyrus were characterized. To obtain an unbiased intraexperimental selection of cells, transgenic mice of the GAD67-eGFP-knock-in-line were at first immunohistochemically validated and finally utilized for electrophysiological and morphological analysis. In GAD67-eGFP-knock-in-mice, the flourescent protein eGFP is expressed in dependency of the GABA-synthesizing enzyme GAD67, which allows an intraexperimental visual identification of interneurons in acute brain slice preparations. For 105 eGFP positive neurons, a morphological characterization as well as the electrophysiological determination of active and passive membrane properties were performed. Furthermore, 19 interneurons were three-dimensionally reconstructed utilizing a Neurolucid system.
Qualitative analysis of cell morphology as well as a hierachical cluster analysis based on quantitative parameters derived from reconstructed neurons revealed a classification in five subgroups: BC-cells (axon projections within the granule cell layer), HICAP-cells (axon projections within the inner molecular layer), HIPP-cells (axon projections within the middle an outer molecular layer), TML-cells (axon projections within the entire molecular layer) and ML-cells (axon projections and soma location within the nolecular layer). This classification is primarily based on the layer specificity of axon projections and suggests a sophisticated inhibitory control of principal cell compartments (somas vs. dendrites) and input tracts (perforant pathway vs. associative pathway) of the dentate gyrus. Regarding the electrophysiological paramters, characteristic firing patterns and significantly different active and passive membrane properties between morphologically defined interneuron classes were observed. A hierachiacal cluster analysis based on electrophysiological parameters of 65 interneurons revealed a seggregation in subgroups similar to the results of the morphological classification. Hence, the interneurons of the dentate gyrus can be classified in five distinct subgroups, defined by their morphology and electrophysiological properties. These classes may execute different functional roles within the circuitry of the dentate gyrus
Mechanisms of optimised plasticity : training associated enhancement of transplant-mediated brain repair in a rodent model of Huntington's disease
No full textEvidence for a link of COVID-19-associated long-term neurologic symptoms and altered brain integrity?
No full textDisplaying the autonomic processing network in humans – a global tractography approach
No full textRegulation of the internal homeostasis is modulated by the central autonomic system. So far, the view of this system is determined by animal and human research focusing on cortical and subcortical grey substance regions. To provide an overview based on white matter architecture, we used a global tractography approach to reconstruct a network of tracts interconnecting brain regions that are known to be involved in autonomic processing. Diffusion weighted imaging data were obtained from subjects of the human connectome project (HCP) database. Resulting tracts are in good agreement with previous studies assuming a division of the central autonomic system into a cortical (CAN) and a subcortical network (SAN): the CAN consist of three subsystems that encompass all cerebral lobes and overlap within the insular cortex: a parieto-anterior-temporal pathway (PATP), an occipito-posterior-temporo-frontal pathway (OPTFP) and a limbic pathway. The SAN on the other hand connects the hypothalamus to the periaqueductal grey and locus coeruleus, before it branches into a dorsal and a lateral part that target autonomic nuclei in the rostral medulla oblongata. Our approach furthermore reveals how the CAN and SAN are interconnected: the hypothalamus can be considered as the interface-structure of the SAN, whereas the insula is the central hub of the CAN. The hypothalamus receives input from prefrontal cortical fields but is also connected to the ventral apex of the insular cortex. Thus, a holistic view of the central autonomic system could be created that may promote the understanding of autonomic signaling under physiological and pathophysiological conditions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
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