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Sciences, Technologie, Santé Mathilde Metna-Laurent SPECIFICITE DU

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Sciences, Technologie, Santé Mathilde Metna-Laurent SPECIFICITE DU Université Bordeaux Segalen Année 2012 Thèse n° 1928 THÈSE pour le DOCTORAT DE L’UNIVERSITÉ BORDEAUX 2 Mention : Sciences, technologie, santé Option : Neurosciences Présentée et soutenue publiquement le 26 juin 2012, par Mathilde Metna-Laurent Née le 19 mars 1984 à Creil, France SPECIFICITE DU TYPE CELLULAIRE DANS LE CONTROLE DES FONCTIONS DE MEMOIRE PAR LES RECEPTEURS CANNABINOIDES CB 1 Membres du Jury Dr Christian Giaume Paris, France ................................ ................................Président, Rapporteur Pr Manuel Guzmán Madrid, Espagne ................................ .................. Rapporteur Dr Aline Desmedt Bordeaux, France ................................ ...........................Examinatrice Dr Pier Vincenzo Piazza Bordeaux, France................................ ........................Examinateur Dr David Robbe Barcelone, Espagne ................................ ................................Examinateur Dr Stéphane Oliet Bordeaux, France ................................ ................................Examinateur invité Dr Giovanni Marsicano Bordeaux, France ................................ ........................Directeur de thèse University Bordeaux Segalen 2012 Thesis n° 1928 THESIS For the DOCTORATE OF BORDEAUX 2 UNIVERSITY Speciality : Sciences, technologie, santé Option : Neurosciences Presented and defended publicly on June 26 th 2012, by Mathilde Metna-Laurent Born on Marsh 19 th 1984 at Creil, France CELL TYPE -SPECIFIC CONTROL OF MEMORY FUNCTIONS BY CB 1 CANNABINOID RECEPTORS Members of the Jury Dr Christian Giaume Paris, France ................................ ................................Chairman, Reviewer Pr Manuel Guzmán Madrid, Espagne ................................ ................................Reviewer Dr Aline Desmedt Bordeaux, France ................................ ................................Examiner Dr Pier Vincenzo Piazza Bordeaux, France ................................ ........................Examiner Dr David Robbe Barcelone, Espagne ................................ ................................Examiner Dr Stéphane Oliet Bordeaux, France ................................ ................................Invited examiner Dr Giovanni Marsicano Bordeaux, France ................................ ........................Thesis supervisor REMERCIEMENTS Tout d’abord merci à Aline Desmedt, Christan Giaume, Manuel Guzmán, Stéphane Oliet et David Robbe pour avoir accepté d’accorder votre temps et votre expertise à l’évaluation de ce travail. Merci à Pier Vincenzo Piazza d’avoir accepté de participer à cette commission, et, en tant que directeur du NeuroCentre Magendie, merci de m’avoir permis de travailler dans des conditions matérielles exceptionnelles. Cette thèse est le fruit d’un travail collectif dont Giovanni Marsicano est le superviseur. Gio, merci de m’avoir accueilli dans ton équipe et de m’avoir fait confiance pour la réalisation de ce projet. Je mesure l’immense chance que j’ai eu d’être formée par un chercheur dont l’excellence scientifique n’a d’égale que les qualités humaines. Je tiens à remercier tout particulièrement les docteurs Pauline Lafenêtre, Joana Lourenço et Francis Chaouloff. Votre soutien permanent durant ces années a conditionné le prologue ainsi que le bon déroulement des peripéties de cette aventure. Merci à toute l’équipe Marsicano, qui malgré la croissance fulgurante de son effectif, a toujours gardé sa cohésion et sa bonne humeur. Bien que les listings soient un peu ennuyeux, « un Marsicano » se laisse difficilement citer sans son voisin. Ainsi, merci à Dany, Peggy, Astrid, Sarah, Barbara, Elodie, Tifany, Isabel, Bo, Aya, Theresa, Ilaria, Luigi, Edgar, Little Giovanni, Michelangelo, Etienne, Federico, Arnau… Je n’oublie pas Pierrick, Martina et Laurie: merci d’avoir partagé mon travail pour un temps, je vous souhaite le meilleur! Mes remerciements s’adressent également à Xia Zhang, ainsi qu’à tous nos collaborateurs cannadiens, de Chine, d’Espagne, de France et de Navarre, avec qui j’ai participé à une expérience collaborative hors du commun, et qui a éveillé ma curiosité pour ces cellules outsiders… Merci à Carsten Wotjak de m’avoir accueillie dans son équipe durant ces semaines de training à la microdialyse et au breakfast bavarois. Merci pour ton soutien et pour avoir apporté, à de nombreuses reprises, ton regard d’expert sur mes résultats. Merci également à Elmira, Linda, Vincenzo et toute l’équipe du « Max Planck » pour leur accueil chaleureux. Un clin d’œil à mes neurocopines, Amélie, Aurore et Marion. J’espère que l’on aura toujours l’occasion de partager ces bons moments de science de comptoir… Merci enfin à toute ma famille et mes amis, les Aquitains, les Picards, les Champenois, les Limousins, la Languedocienne, les Franciliens… Un immense merci à ma sœur et à ma maman pour leur soutien et leur amour inconditionnel. Merci à toi pour qui l’anonymat est un droit non négociable : ce travail est en partie anonyme. LIST OF PUBLICATIONS • Articles published or in process of publication in peer reviewed scientific journals: Boucher AA, Vivier L, Metna-Laurent M , Brayda-Bruno L, Mons N, Arnold JC, Micheau J (2009) Chronic treatment with Delta(9)-tetrahydrocannabinol impairs spatial memory and reduces zif268 expression in the mouse forebrain . Behavioral Pharmacology 20(1):45-55. Dubreucq S, Kambire S, Conforzi M, Metna-Laurent M , Cannich A, Soria-Gomez E, Richard E; Marsicano G, Chaouloff F (2012). CB1 receptors located on sim1-expressing neurons control emotional behaviors . Neuroscience 204:230-244. Bénard G 1, Massa F 1, Puente N, Lourenço J, Bellocchio L, Soria-Gómez E, Matias I, Delamarre A, Metna-Laurent M , Cannich A, Hebert-Chatelain E, Mulle C, Ortega-Gutiérrez S, Martín-Fontecha M, Klugmann M, Guggenhuber S, Lutz B, Gertsch J, Chaouloff F, López-Rodríguez ML, Grandes P, Rossignol R, Marsicano G (2012) Mitochondrial CB(1) receptors regulate neuronal energy metabolism . Nature Neuroscience 15(4):558-564. Han J 1, Kesner P 1, Metna-Laurent M 1, Duan T, Xu L, Georges F, Koehl M, Abrous DN, Mendizabal-Zubiaga J, Grandes P, Liu Q, Bai G, Wang W, Xiong L, Ren W, Marsicano G 2, Zhang X2 (2012) Acute Cannabinoids Impair Working Memory through Astroglial CB1 Receptor Modulation of Hippocampal LTD . Cell 148, 1039-1050. Metna-Laurent M 1, Soria-Gόmez E 1, Verrier D, Conforzi M, Jégo P, Lafenêtre P, Marsicano G (2012) Bimodal Control of Fear-Coping Strategies by CB1 Cannabinoid Receptors . The Journal of Neuroscience, in press . • Oral communications Metna-Laurent M , Jégo P, Conforzi M, Lafenêtre P, Marsicano G The endocannabinoid system bidirectionally determines fear-coping strategies. Meeting of the Université franco- allemande, Deutsch-Französische Hochschule, Munich, Germany, 2011 July 13 th -14 th . Metna-Laurent M , Han J, Kesner P, Duan T, Xu L, Georges F, Koehl M, Abrous DN, Mendizabal-Zubiaga J, Grandes P, Liu Q, Bai G, Wang W, Xiong L, Ren W, Marsicano G, Zhang X. Astroglial CB1 receptors and memory . 2 nd Symposium of the NeuroCentre Magendie, Bordeaux, France, 2011 December 15 th -16 th ; International Astrocytes Summer school, Bertinoro, Italy, 2012 Marsh 25 th -31 th . 1 Share first authorship 2 Share last authorship • Posters Metna-Laurent M , Lafenêtre P, Marsicano G Role of the endocannabinoid system in the associative components of extinction. Annual meeting of the Network of European Neuroscience Institutes. Fodelebeach, Greece, 2009 May 20 th -21 st ; 9th meeting of the French Neurosciences Society. Bordeaux, France, 2009 May 26 th -29 th . Metna-Laurent M , Lafenêtre P, Marsicano G Role of the endocannabinoid system in fear- induced avoidance behaviors. Gordon Research Conference on Amygdala in Health and Disease. Colby College, Waterville, ME, USA, 2009 July 12 th -17 th . Metna-Laurent M , Lafenêtre P, Jégo P, Marsicano G Bimodal control of fear-coping strategies by the endocannabinoid system. 40 th Annual meeting of the Society for Neuroscience. San Diego, CA, USA, 2010 November 13 th -17 th . Metna-Laurent M , Lafenêtre P, Jégo P, Conforzi M, Marsicano G The endocannabinoid system bidirectionally determines fear-coping strategies. Gordon Research Conference on Cannabinoid functions in the CNS. Les Diablerets, Switzerland, 2011, May 22 th -27 th . Conforzi M, Metna-Laurent M , Wiesner T, Bosier B, Massa F, Marsicano G Implication of astrocytic CB 1 receptors in fear memory. Gordon Research Conference on Cannabinoid functions in the CNS. Les Diablerets, Switzerland, 2011, May 22 th -27 th . Metna-Laurent M , Soria-Gomez E, Verrier D, Jégo P, Conforzi M, Lafenêtre P, Marsicano G nd Bimodal control of fear-coping strategies by CB 1 cannabinoid receptors. 2 symposium of the NeuroCentre Magendie, Bordeaux, France, 2011 December 15 th -16 th . • Scientific article for the general public Metna-Laurent M, Marsicano G (2012) Cannabis et mémoire de travail . La Recherche, in press. Address of the laboratory: NeuroCentre Magendie INSERM U862 group « Endocannabinoid and NeuroAdaptation » 146, rue Léo Saignat 33077 Bordeaux Cedex RESUME Le système endocannabinoïde est un important modulateur des fonctions physiologiques. Dans le cerveau, son contrôle s’exerce essentiellement par les récepteurs cannabinoïdes de type 1 (CB 1). Les récepteurs CB 1 sont abondamment exprimés sur les neurones excitateurs glutamatergiques et les neurones inhibiteurs GABAergiques et leur stimulation inhibe la libération du glutamate et du GABA. Récemment, l’activité des récepteurs CB1 sur les astrocytes a été proposée comme facilitant
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