Première évaluation de l’intégralité des propriétés synaptiques des terminaisons en compétition lors du développement de la jonction neuromusculaire

La compétition synaptique est un processus fondamental du développement du système nerveux qui permet la mise en place de circuits neuronaux fonctionnels et fiables. Les processus qui le sous-tendent sont multiples et complexes, et leur étude dans le SNC est compliquée par la taille et l’accessibilité réduites des structures d’intérêt. Par contre, la JNM offre un environnement favorable qui permet la mise en place de conditions expérimentales robuste où ces processus peuvent être sondés. La caractérisation de ces processus permettrait de mieux comprendre la physiopathologie de plusieurs maladies neuromusculaires. De plus, elle permettrait d’améliorer significativement nos chances de comprendre les processus correspondant au niveau du SNC en fournissant de nouvelles hypothèses à tester. Par contre, le développement de protocoles expérimentaux pour étudier la compétition synaptique à la JNM demeure difficile. Les processus qui influencent la compétition et les propriétés des terminaisons sont interdépendants et l’incapacité de mesurer simultanément ces propriétés représente une contrainte majeure. L’objectif de ce projet de recherche était de développer des outils afin de mieux mesurer et caractériser les propriétés synaptiques des terminaisons en compétition à la JNM en développement et d’utiliser ces outils afin de mieux comprendre la dynamique de la compétition. Nous avons été en mesure de caractériser la relation entre la facilitation et la probabilité de relâche à la JNM. Puisque la facilitation et le contenu quantique peuvent être mesurés simultanément, cette relation permet de connaître le ratio de force synaptique et de probabilité de relâche entre les terminaisons. Nous montrons aussi que ces informations permettent de déduire le ratio de leur couverture territoriale. Ensemble, ces résultats représentent la première évaluation simultanée et intégrale des propriétés synaptiques des terminaisons en compétition à des jonctions neuromusculaires en développement. Ensuite, nous avons utilisé ces outils afin d’évaluer la relation entre ces différents paramètres synaptiques. D’abord, nous avons pu conclure que les ratios de probabilité de relâche et de couverture territoriale ont peu de corrélation avec les ratios de force synaptique dans les stades initiaux de la compétition, mais qu’une corrélation plus forte s’installe lorsqu’une des terminaisons devient au moins deux fois plus forte que sa compétitrice. De plus, nos données suggèrent que la probabilité de relâche et la couverture territoriale sont toutes deux régulées de manière dynamique au cours du processus. Finalement, nos données suggèrent que l’importance relative des ratios de probabilité de relâche et de couverture territoriale dans la détermination des ratios de force synaptique reste constante au cours du processus et que cette importance est équivalente.Synaptic competition is a fundamental process of development of the nervous system that allows the establishment of functional and reliable neural circuits. The processes that underlie it are multiple and complex, and their study in the CNS is complicated by the size and reduced accessibility of the structures of interest. On the other hand, the neuromuscular junction offers a favorable environment that allows the setting up of robust experimental conditions where these processes can be probed. The characterization of these processes would lead to a better understanding of the pathophysiology of several neuromuscular diseases. In addition, it would significantly improve our chances of understanding CNS-level processes by providing new hypotheses to test. On the other hand, the development of experimental protocols to study synaptic competition at the JNM remains difficult. The processes that influence competition and the properties of synaptic inputs are interdependent and the inability to simultaneously measure these different synaptic properties is a major constraint. The objective of this research project was to develop tools to better measure and characterize the synaptic properties of competing endings at the developing NMJ and to use these tools to better understand the dynamics of competition. We were able to characterize the relationship between facilitation and release probability at the NMJ. Since facilitation and quantum content can be measured simultaneously, this relationship allows for knowledge of synaptic inputs strength and release probability ratios. We also show this information can be used to deduce the ratio of their territorial coverage. Together, these results represent the first simultaneous and integral evaluation of the synaptic properties of competing inputs at developing neuromuscular junctions. We further used these tools to evaluate the relationship between the different synaptic parameters. First, we were able to conclude that the release probability and territorial coverage ratios have little correlation with synaptic strength ratios in the initial stages of competition, but that a stronger correlation occurs when one input becomes at least twice as strong as his competitor. In addition, our data suggest that the release probability and the territorial coverage are both dynamically regulated during the process. Finally, our data suggest that the relative importance of release probability and territorial coverage ratios in the determination of synaptic strength ratios remains constant throughout the process and that this importance is equivalent

Global standards of Constitutional law : epistemology and methodology

Just as it led the philosophy of science to gravitate around scientific practice, the abandonment of all foundationalist aspirations has already begun making political philosophy into an attentive observer of the new ways in which constitutional law is practiced. Yet paradoxically, lawyers and legal scholars are not those who understand this the most clearly. Beyond analyzing the jurisprudence that has emerged from the expansion of constitutional justice, and taking into account the development of international and regional law, the ongoing globalization of constitutional law requires comparing the constitutional laws of individual nations. Following Waldron, the product of this new legal science can be considered as ius gentium. This legal science is not as well established as one might like to think. But it can be developed on the grounds of the practice that consists in ascertaining standards. As abstract types of best “practices” (and especially norms) of constitutional law from around the world, these are only a source of law in a substantive, not a formal, sense. They thus belong to what I should like to call a “second order legal positivity.” In this article I will undertake, both at a methodological and an epistemological level, the development of a model for ascertaining global standards of constitutional law

Invisible Diaspora?:English Ethnicity in the United States before 1920

The article presents an examination into the English population of the United States during the 19th and early 20th centuries, examining their ethnic identity as a diaspora community. Introductory details are given noting the relative lack of attention given to English Americans as an ethnic group. Topics addressed include reasons behind the invisibility of the English immigrant identity in the U.S., the existence of English ethnic organizations, and an overview of their activities