1,720,963 research outputs found
The synaptic split of snap-25: different roles in glutamatergic and gabaergic neurons
No full textCarlotta Grumelli THE SYNAPTIC SPLIT OF SNAP-25: DIFFERENT ROLES IN GLUTAMATERGIC AND GABAERGIC NEURONS? Previous studies (Verderio et al., 2004; Frassoni et al., 2005) have demonstrated a different sensitivity of GABAergic and glutamatergic neurons to the action of Botulinum toxins A and E (BoNT/A and E); during my PhD period, I aimed at specifically addressing the reasons at the basis of the lower efficacy of BoNT/A or BoNT/E at GABAergic terminals. To clarify this issue, the penetration, the route of entry and the persistence of BoNTs in excitatory and inhibitory cultured hippocampal neurons have been investigated in detail. I demonstrated that the preferential action of BoNT/A at excitatory synapses does not result from either the absence of BoNT receptors in interneurons, which may lead to a defective toxin penetration, or a different route of entry in inhibitory neurons; I also showed that the variable efficiency of BoNT/A and BoNT/E on different type of neurons is not to be ascribed to a defective toxin persistence in GABAergic cells. Finally, I demonstrated that exogenous expression of SNAP-25 into inhibitory neurons makes GABAergic vesicle recycling sensitive to BoNT/A, thus suggesting the possibility that the amount of SNAP-25 and not the toxin penetration is at the basis of the different effects of the two neurotoxins at excitatory or inhibitory terminals. Exogenously expressed SNAP-25 might substitute a putative, endogenous SNARE, resistant to BoNT/A action, thus making the exocytosis at inhibitory terminals sensitive to BoNT/A. These putative SNAP-25 neuronal isoforms includes SNAP-29 and SNAP-47. To get insights into the possibility that these isoforms may support exocytosis in inhibitory neurons, in the last part of my PhD period, I analyzed the expression of different SNAP-25 isoforms in GABAergic and glutamatergic neurons
Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations
Get PDFSNAP-25 is a SNARE protein implicated in exocytosis and in the negative modulation of voltage-gated calcium channels. We have previously shown that GABAergic synapses, which express SNAP-25 at much lower levels relative to glutamatergic ones, are characterized by a higher calcium responsiveness to depolarization and are largely resistant to botulinum toxin A. We show here that silencing of SNAP-25 in glutamatergic neurons, a procedure which increases KCl-induced calcium elevations, confers these synapses with toxin resistance. Since it is known that calcium reverts the efficacy of botulinum A, we investigated whether the lower effectiveness of the toxin in inhibiting GABAergic vesicle cycling might be attributable to higher evoked calcium transients of inhibitory neurons. We demonstrate that either expression of SNAP-251-197 or BAPTA/AM treatment, both inhibiting calcium dynamics, facilitate block of GABAergic vesicle exocytosis upon toxin treatment. These data indicate that intrinsic calcium dynamics control botulinum A susceptibility in distinct neuronal populations
Analysis of SNAP-25 immunoreactivity in hippocampal inhibitory neurons during development in culture and in situ
No full textSynaptosomal associated protein of 25 kDa (SNAP-25) is a component of the soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complex which plays a central role in synaptic vesicle exocytosis. We have previously demonstrated that adult rat hippocampal GABAergic synapses, both in culture and in brain, are virtually devoid of SNAP-25 immunoreactivity and are less sensitive to the action of botulinum toxin type A, which cleaves this SNARE protein [Neuron 41 (2004) 599]. In the present study, we extend our findings to the adult mouse hippocampus and we also provide demonstration that hippocampal inhibitory synapses lacking SNAP-25 labeling belong to parvalbumin-, calretinin- and cholecystokinin-positive interneurons. A partial colocalization between SNAP-25 and glutamic acid decarboxylase is instead detectable in developing mouse hippocampus at PO and, at a lesser extent, at P5. In rat embryonic hippocampal cultures at early developmental stages, SNAP-25 immunoreactivity is detectable in a percentage of GABAergic neurons, which progressively reduces with time in culture. Consistent with the presence of the substrate, botulinum toxin type A is partially effective in inhibiting synaptic vesicle recycling in immature GABAergic neurons. Since SNAP-25, beside its role as a SNARE protein, is involved in additional processes, such as neurite outgrowth and regulation of calcium dynamics, the presence of higher levels of the protein at specific stages of neuronal differentiation may have implications for the construction and for the functional properties of brain circuits. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved
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
Internalization and mechanism of action of clostridial toxins in neurons
No full textBotulinum toxins are metalloproteases that act inside nerve terminals and block neurotransinitter release via their activity directed specifically on SNARE proteins. This review summarizes data on botulinuin toxin modes of binding, sites of action, and biochemical activities. Their use in cell biology and neuroscience is considered, as well as their therapeutic utilization in human diseases characterized by hyperfunction of cholinergic terminals. (c) 2005 Elsevier Inc. All rights reserved
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
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