1,720,964 research outputs found
Specification and integration of interneuron subtypes in the neocortex
No full textCortical microcircuit function relies on the coordinated activity of a large diversity of interneuron (IN) subtypes. These cells originate from discrete areas of the subpallium, namely the medial and caudal ganglionic eminences (MGE and CGE) and the preoptic area (POA). From these sites of origin, INs migrate long distances to reach the developing neocortex and integrate into the cortical microcircuits. Understanding the emergence of their molecular diversity and how they develop in the neocortex will provide important insights on the architecture of the mature circuit in health and disease. In my PhD project, I studied molecular mechanisms controlling the specification, migration and maturation of IN subclasses. In the first study, I aimed at identifying the developmental origin of a specific subclass of cortical IN called neurogliaform cells (NGCs). These cells are recruited by long-range connections, such as interhemispheric and thalamic projections, and are thought to be the effectors of a powerful inhibitory circuit by activating metabotropic GABAB receptors. Using in vivo lineage-tracing in mice, I found that NGCs originate from a pool of cells located in the POA, co-expressing the transcription factor Hmx3 and the serotonin receptor 3A (HTR3A). Through a combination of methods, I found that Hmx3-derived HTR3A+ cortical IN exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory. In the second study, I focused on mechanisms regulating laminar allocation of superficial neocortical INs. In a previous study, we found that HTR3A controls the migration and laminar positioning of superficial cortical INs, but molecular mechanisms remain unknown. Using a microarray screen on wild-type and Htr3a-KO INs, I identified PlexinA4 (PlxnA4) as a candidate gene possibly acting downstream the Htr3a and specifically upregulated during the phase of cortical plate invasion. Using in vitro and in vivo strategies, I found that PLXNA4 ligand SEMA3A has chemorepulsive effect on PLXNA4+/HTR3A+ superficial INs and that these effects are mediated by the PLXNA4/NRP1 receptor complex. Interestingly, SEMA3A was found to be secreted by deep layer INs, which do not express the HTR3A. Overall, these results suggest a new guidance mechanism for migrating HTR3A+ INs, involving a HTR3A-dependent upregulation of PLXNA4 in superficial cortical INs. These PLXNA4+/HTR3A+ cells will become gradually sensitive to the repulsive ligand SEMA3A, secreted by deep layer INs, and will preferentially settle into superficial ones. In the third study, I aimed at characterizing the role of the potassium/chloride cotransporter KCC2 in INs at early developmental stages. KCC2 plays a main role in driving GABAAR-mediated inhibition in the mature cortex, by tuning intracellular chloride concentration. Interestingly, it is upregulated in INs earlier than in excitatory cells. To determine the role of KCC2 in IN development, I aimed to selectively knock-out this cotransporter in cortical INs using cre-lox approach. Analyses of the somatosensory cortices indicated that IN-specific deletion of KCC2 significantly decreased the density of parvalbumin (PV)-expressing cells in recombined mice and non cell-autonomously affected the morphological maturation of pyramidal neurons. These results suggest an important role for KCC2 in the maturation of PV-expressing INs. Taken together, studies performed in this PhD thesis provide new insight on molecular mechanisms regulating the specification, migration and laminar allocation of cortical INs
Investigating the expression and function of CGE-derived interneurons
No full textGABAergic interneurons (INs) account for about 20-30% of the whole neuronal population in the neocortex and are crucial to establish inhibitory modulation in cortical microcircuits. A wide diversity of cortical interneuron subtypes are described in the neocortex and developmental studies have provided new insights on the classification of cortical interneuron subtypes. During development, cortical INs originate from distinct areas of the subpallium, more specifically from the medial (MGE) and caudal (CGE) ganglionic eminences. After their generation, from these specific subregions they first tangentially migrate into the pallium and then invade the cortical plate..
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins
No full textThe establishment of neuronal circuits requires neurons to develop and maintain appropriate connections with cellular partners in and out the central nervous system. These phenomena include elaboration of dendritic arborization and formation of synaptic contacts, initially made in excess. Subsequently, refinement occurs, and pruning takes places both at axonal and synaptic level, defining a homeostatic balance maintained throughout the lifespan. All these events require genetic regulations which happens cell-autonomously and are strongly influenced by environmental factors. This review aims to discuss the involvement of guidance cues from the Semaphorin family.UPMCCAB
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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