Impact of Open Channel Blockers on the Surface Dynamics and Organization of NMDA Receptors Alexandra Fernandes

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Impact of Open Channel Blockers on the Surface Dynamics and Organization of NMDA Receptors Alexandra Fernandes Impact of open channel blockers on the surface dynamics and organization of NMDA receptors Alexandra Fernandes To cite this version: Alexandra Fernandes. Impact of open channel blockers on the surface dynamics and organization of NMDA receptors. Neurons and Cognition [q-bio.NC]. Université de Bordeaux, 2020. English. NNT : 2020BORD0181. tel-03177416 HAL Id: tel-03177416 https://tel.archives-ouvertes.fr/tel-03177416 Submitted on 23 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE PRÉSENTÉE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE BORDEAUX ÉCOLE DOCTORALE Sciences de la Vie et de la Santé SPÉCIALITÉ Neurosciences Par Alexandra FERNANDES Impact of open channel blockers on the surface dynamics and organization of NMDA receptors Sous la direction de Julien DUPUIS Soutenue le 10 Novembre 2020 Membres du jury : Mme SANS, Nathalie Directeur de recherche INSERM Président M. DE KONINCK, Paul Professeur, University of Laval Rapporteur Mme LÉVI, Sabine Directeur de recherche CNRS Rapporteur Mme CARVALHO, Ana Luísa Professeur, University of Coimbra Examinateur M. DUPUIS, Julien Chargé de recherche INSERM Directeur THÈSE PRÉSENTÉE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE BORDEAUX ÉCOLE DOCTORALE Sciences de la Vie et de la Santé SPÉCIALITÉ Neurosciences Par Alexandra FERNANDES Impact des bloqueurs de canal ouvert sur la dynamique et l’organisation de surface des récepteurs NMDA Sous la direction de Julien DUPUIS Soutenue le 10 Novembre 2020 Membres du jury : Mme SANS, Nathalie Directeur de recherche INSERM Président M. DE KONINCK, Paul Professeur, University of Laval Rapporteur Mme LÉVI, Sabine Directeur de recherche CNRS Rapporteur Mme CARVALHO, Ana Luísa Professeur, University of Coimbra Examinateur M. DUPUIS, Julien Chargé de recherche INSERM Directeur Insane in the membrane Insane in the brain - Cypress Hill, 1993 Acknowledgements I would like to thank first the members of my thesis committee for accepting to judge this doctoral work: Paul de Koninck, Sabine Lévi, Ana Luísa Carvalho and Nathalie Sans. I am honored to have such a high standard for excellence in my jury panel. I am grateful for the financial support of the Minstére Francais pour de l’Education Supérieure, Recherche et Innovation and the Fondation pour la Recherche Médicale, who awarded me a salary throughout my doctorate. I would like to acknowledge the institutions which scaffolded this project, namely the IINS and the BIC. Within these institutions, I would like to leave a special thanks to Remi Galland, to the culture team, and to all of the technical support group of the BIC, with special thanks to the contributions of Christel Poujol and Magali Mondin. I would equally like to acknowledge the CNRS, and, chiefly, the University of Bordeaux, for managing the administrative burden of my doctoral path. I would first like to personally thank Dr. Laurent Groc for welcoming me into his team, and all the stimulating exchanges we have had during these years. Thank you for seeking and supporting new ideas, and for being so constructive and supportive during every discussion. I would like to thank all the members of the Groc Team with whom I had the pleasure of sharing this journey. A special thanks to Julie Jézéquel, who started this project and brilliantly developed its foundations. A special thanks also to Julien Dupuis, Nathan Bénac, Delphine Bouchet, “Paulinette” Durand and Hélène Gréa, who directly contributed to this project. A last special thanks to Julien Dupuis, Delphine Bouchet, Emily Johansson and Joana Ferreira, for providing training and support on techniques I had never worked with before. Finally, I would like to thank all other past and present members of the Groc team: Constance, Théo, Elodie, Mar, Diego, Frédéric, Daniel, Zoë, Stephane, Elise, Ezequiel, TingTing, Blanka, Pauline, François, Elena, Charlotte, Laetitia, Audrey, Marylin, Silvia, Sebastien, Rachel, Nila, Marion V., Marion F., Jeremy, Pierre … I’m terribly sorry if I am forgetting someone! Now for the tough part! I would like to give the biggest THANK YOU in these acknowledgements to my supervisor, Dr. Julien Dupuis. For having been the example of availability, dedication, support and attentiveness during 5 years, while having had the work of not only cultivating me scientifically, but also of putting up with my shortcomings. Thank you so very much, boss, for being a mentor and a friend. I would like to also leave a mention here (another mention is in the Portuguese section) to my good friend Joana Ferreira, who aided me with various “existential” scientific questions, most of which were resolved through the drawing of various circles of different shapes, sizes and colors on the back of pieces of scrap paper which I have kept and cherished. You made what seemed impossible to understand easy to read and taught me how to think more flexibly. Before entering the Portuguese section, I would like to thank all my international friends at the Neurocampus, especially Cynthia, Vladimir, Pascal and Ashley, Dario “vafanapoli”, Tomasito tomatito and Julio “quiquitapegando”, who were too close to avoid sharing coffees and bad jokes with me. Agora é que é! Acredito que a família vem em primeiro lugar, portanto quero agradecer principalmente ao meu pai e à minha mãe, que eu amo profunda e incondicionalmente, e que me abençoaram com o seu imenso amor e uma base firme sobre a qual pude crescer. À minha irmã, que tem metade do meu coração, que é a melhor irmã de sempre, e foi, até há bem pouco tempo, a noiva mais linda à face da terra. Ao meu namorado João, que tem a outra metade do meu coração, que passou pela provação de um relacionamento à distância durante 5 anos por mim. À minha querida avó Marlene, que me criou e me ligou tantas vezes só para saber como eu estava e se estava a chover na França, com uma persistência inabalável, testemunho de uma força à qual eu almejo. Ao avô Artur, à avó Margarida, e ao avô Henrique, que são uns jovens por dentro. A todos os meus tios e tias, primos e primas. Este doutoramento também é vosso, que participaram na minha formação para a vida. Aos meus “docinhos”, Sofia Saraiva e Andreia Dias. A amizade e respeito que tenho por vocês continua a crescer desde que entraram na minha vida em 2011. Voltava com vocês para a ilha amanhã. Finalmente, ao “irmão” Ricardo Abreu, o meu “choco” (eheh). Alors, se me perguntassem como é que foi possível preservar a minha alma em formato de galo de Barcelos e não perder nenhum vernáculo de vulgaridades em 5 anos nesta cidade francesa cinzenta e chuvosa 80% do tempo (Bordeaux)? Eu responderia, como cantou o Ringo Starr, “I get by with a little help from my friends”. Aos Usual Suspects masculinos originais, Doutor José “Jesus Cristo” Cruz, que me batizou Xaninha aos olhos do senhor, sendo o senhor uma garrafa de vinho do Porto, Filipe “Filó/Pipo/1000 alcunhas/Funky dopamina” Nunes Vincente, que me ensinou que o lema para a vida não é hakuna mata, mas sim “é preciso andar sempre ****** todo ****** ”, Tiago “RIP Jean-Pierre” Campelo, só por ser quem é - um grande obrigada por terem tornado estes anos tão divertidos. Nunca passei convosco um momento que não tenha sido divertido. Agora, às meninas com quem partilhei o meu tempo aqui, há tanto para dizer, e tão pouco jeito para tal! À Joana, a coitada que teve que suportar a maior dose de Alexandra Inês, pois era no trabalho, no bar, no consulado, em todo o lado, e volta e meia estavam os meus óculos agarrados a ela e eu no chão à procura deles. Obrigada por teres sido tão minha amiga durante este tempo todo (é que foi mesmo muito!). Ajudaste-me a todos os níveis. És uma pessoa exemplar, e tens um coração enorme. À Inês, a minha jukebox, a tripeira mais bem-educada que a Cidade Invicta já viu, e que me faz rir tanto com a sua espontaneidade, as suas saídas musicais e imitações “spot-on” das gentes do Puorto. À Eva, uma força da natureza, que é a melhor anfitriã de festas improvisadas de sempre. Viva a casa da Eva, vamos aprender a estalar os dedos, vivam os jogos nas camisolas brancas, viva a boa música, vivam as noites sem rótulo. Nunca mudes, Eva! À Tia Elsa, que me deu abrigo quando estava em baixo, que esteve lá para tudo o que desse e viesse. Direi para sempre com orgulho: “Esta é a minha amiga Ânia, ela fala espanhol”. Principalmente quando fores rica. Por favour manda-me a referência do teu sofá que dorme-se lá mesmo bem… Sofá? Ou Sófá? Como é que é Nanci Kinki? Quando é que voltamos a Paris, para vermos o museu de história natural? Para a próxima deixamos o Filó no jardim do museu Rodin! Um beijinho de bolo do caco e um abraço à porta do Berthom para ti. Para acabar, um obrigado à Barbara “you never go if you don’t go” Pinheirinho, por me ter dito para ligar e votar, e por causa dessa participação termos ganho a eurovisão em 2017, ao João “Roger” Covita, por me ter devolvido o guarda-chuva, desejo-lhe boa sorte na sua jornada fitness, e ao Diogo Neto, por se queixar das mesmas coisas que eu, e assim me deixar certa de que está tudo maluco, não sou só eu.
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