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Dissection Électrophysiologique Et Fonctionnelle Des Propriétés Du Réseau Des Ganglions De La Base Corinne Beurrier

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Dissection Électrophysiologique Et Fonctionnelle Des Propriétés Du Réseau Des Ganglions De La Base Corinne Beurrier Dissection électrophysiologique et fonctionnelle des propriétés du réseau des ganglions de la base Corinne Beurrier To cite this version: Corinne Beurrier. Dissection électrophysiologique et fonctionnelle des propriétés du réseau des gan- glions de la base. Neurobiologie. Aix Marseille Université, 2018. tel-02348409 HAL Id: tel-02348409 https://hal.archives-ouvertes.fr/tel-02348409 Submitted on 5 Nov 2019 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. Faculté des Sciences Campus de Luminy Habilitation à Diriger des Recherches Corinne Beurrier Chargée de Recherche au CNRS Dissection électrophysiologique et fonctionnelle des propriétés du réseau des ganglions de la base Soutenue le 14 décembre 2018 devant le jury composé de : Pr. Valéry Matarazzo Président Pr. Stéphane Charpier Rapporteur Dr. Catherine Le Moine Rapportrice Dr. Paul Apicella Rapporteur Dr. Hélène Marie Examinatrice Dr. Lydia Kerkerian Le-Goff Examinatrice SOMMAIRE I. Curriculum Vitae II. Travaux antérieurs III.1 Les propriétés intrinsèques des neurones du noyau subthalamique et l’effet de la stimulation à haute fréquence III.2 La plasticité à long terme dans le noyau accumbens est un support neuronal de la sensibilisation à la cocaïne III.3 L’ablation génétiquement ciblée des neurones striato-nigraux révèle des fonctions très diverses de ces neurones III.4 Les interneurones cholinergiques du striatum sont des acteurs essentiels dans la pathophysiologie de la maladie de Parkinson III. Projet de recherche IV. Références V. Articles I. CURRICULUM VITAE Née le 28 avril 1971 à Libourne (33), France, nationalité française. Adresse professionnelle: Institut de Biologie du Développement de Marseille (IBDM), UMR CNRS 7288 - Aix Marseille Université, Parc scientifique de Luminy, Case 907, 13288 Marseille cedex 9. Tél: +33(0)4 91 26 92 50; Fax: +33(0)4 91 26 92 44 e-mail: [email protected] Situation actuelle: Chargé de Recherche de 1ère classe CNRS à l’IBDM dirigé par le Dr. A Le Bivic, commission 25 : "Neurobiologie moléculaire et cellulaire, neurophysiologie". GRADES UNIVERSITAIRES ET PARCOURS SCIENTIFIQUE • 1993 : Maîtrise de Psychologie Expérimentale, Université de Bordeaux II. Ces quatre années d’étude en psychologie ont été très enrichissantes d’un point de vue personnel. Cependant, ne me projetant pas dans une carrière professionnelle en tant que psychologue, j’ai décidé de changer d’orientation. L’université de Bordeaux offrant l’opportunité aux étudiants en psychologie de s’inscrire dans un cursus neuroscientifique, j’ai saisi cette occasion. • 1994 : Diplôme d’Etudes Approfondies de Neurosciences et Pharmacologie, Universités de Bordeaux I et II. • 1994-1998 : Doctorat Sciences biologiques et médicales, Université de Bordeaux II. J’ai effectué ma thèse dans le laboratoire de Neurophysiologie dirigé par le Dr. B. Bioulac, UMR CNRS 5543. Après mon stage de DEA effectué dans le même laboratoire où j’ai travaillé sur l’effet de la stimulation à haute fréquence du noyau subthalamique chez le singe, j’ai décidé, pour une raison qui m’échappe encore, de faire de l’électrophysiologie in vitro sur des tranches de cerveau. Le noyau subthalamique est resté mon centre d’intérêt et j’ai décortiqué au cours de ma thèse les propriétés intrinsèques de ces neurones par des enregistrements intracellulaires et en patch-clamp. L’électrophysiologie in vitro sur tranches étant une approche nouvelle dans le laboratoire, je dois remercier ici plusieurs personnes sans lesquelles mon parcours scientifique aurait pu s’arrêter là … Particulièrement : Jean-Marc Israel, chercheur travaillant sur les neurones de l’hypothalamus dans le laboratoire de D. Poulain, qui m’a appris l’électrophysiologie ; Jacques Audin, électronicien dans le laboratoire, qui m’a apporté une aide technique (et amicale) inestimable et enfin Constance Hammond qui a co-encadré ma thèse avec Bernard Bioulac. J’ai soutenu mon travail de thèse en novembre 1998. • 1999-2002 : Post-doctorat, Stanford University dans le Nancy Pritzker laboratory dirigé par le Dr. Robert.C. Malenka, Department of Psychiatry and Behavioral Sciences, School of Medicine. J’ai décidé d’explorer le monde de la synapse que je n’avais pas du tout abordé au cours de ma thèse chez Robert C. Malenka qui venait de s’installer à l’université de Stanford après avoir travaillé de nombreuses années dans le laboratoire de Roger Nicoll. J’ai travaillé principalement sur l’effet de la cocaïne sur la transmission glutamatergique dans le noyau accumbens. Nous avons montré que la dépression à long terme entre les synapses du cortex pré-frontal et les neurones de projection du noyau acccumbens pouvait être un des substrats neuronaux de la sensibilisation à la cocaïne. 1 • 2002-2003 : Post-doctorat, Institut de Neurobiologie de la Méditerranée (INMED) dirigé par le Dr. Y. Ben-Ari, INMED - INSERM U29, Marseille. Après mon post-doc, j’ai décidé d’intégrer l’équipe de Constance Hammond avec qui j’avais travaillé pendant ma thèse. J’ai ainsi rejoint l’INMED qui venait tout juste de s’installer à Marseille. J’ai développé au cours de ces années une préparation permettant de conserver le réseau des ganglions de la base in vitro. • 2003 : Recrutée au CNRS en tant que chargé de recherche de 2ième classe par la commission 24 "Interactions cellulaires". Affectée à l’Institut de Neurosciences de la Méditerranée (INMED) dirigé par le Dr. Y. Ben-Ari, INSERM U29, Marseille. • 2003-2006 : J’ai poursuivi le travail entamé pendant mon post-doc toujours dans l’équipe de Constance Hammond à l’INMED. • 2006 - présent : en 2006, Lydia Kerkerian m’a accueillie dans son équipe "Interactions Cellulaires, Neurodégénérescence et Neuroplasticité" installée depuis peu à l’Institut de Biologie du Développement de Marseille (IBDM, UMR CNRS 6216 - Aix Marseille Université) dirigé à l’époque par le Dr. Geneviève Rougon et actuellement par le Dr. André Le Bivic. En 2007, j’ai été promue au grade de chargé de recherche de 1ère classe. La thématique de l’équipe se focalise sur la fonction des ganglions de la base dans un contexte normal et pathologique, particulièrement la maladie de Parkinson. A mon arrivée, j’ai travaillé en étroite collaboration avec Paolo Gubellini sur des projets en cours dans le laboratoire s’attachant à décrire le rôle des transporteurs et des récepteurs métabotropiques du glutamate dans un contexte parkinsonien. Depuis quelques années, je développe ma propre thématique au sein du laboratoire que j’exposerai plus en détail dans ce manuscrit. ENCADREMENT • Delphine Révy : Master 2 Biologie des Eucaryotes, Aix-Marseille Université, 2007-2008. Delphine a caractérisé les effets d’un nouvel agoniste orthostérique des récepteurs mGlu4 au niveau de la synapse striato-pallidale. Ce travail s’inscrivait dans une collaboration plus large impliquant J-P Pin, F. Acher et M. Amalric sur le potentiel thérapeutique de nouvelles molécules agissant sur les récepteurs mGlu dans la maladie de Parkinson. • Delphine Révy : Thèse de doctorat Aix-Marseille Université, Spécialité : Neurosciences, 2008-2012. Delphine a décidé de rester faire sa thèse dans le laboratoire après avoir obtenu une bourse du ministère de l’Enseignement Supérieur et de la Recherche et a été ma première étudiante en thèse. Elle a caractérisé d’un point de vue cellulaire et comportemental un modèle de souris transgénique que j’ai créé en collaboration avec le Dr. Hélène Marie permettant l’ablation spécifique des neurones striato-nigraux. • Latéfa Yekhlef : Master 2 Neurosciences Aix-Marseille Université, Spécialité : cellulaire et moléculaire, 2011-2012. Latéfa est arrivée au laboratoire au moment où je développais l’optogénétique. Elle a testé les effets de deux types d’opsines, la channelrhodopsine (activation) et l’halorhodopsine (inhibition), sur l’activité électrique de la population que nous voulions cibler : les interneurones cholinergiques du striatum. • Florence Jaouen : Ingénieur de recherche en CDD de 2011 à 2016. Nous avons recruté Florence grâce à l’ANR que nous avions obtenu en 2011. Florence a énormément contribué à la mise en place de la technique d’optogénétique grâce à ses compétences en biologie moléculaire et cellulaire. • Marion Deroche : Etudiante en Licence 3 Sciences de la vie, Aix-Marseille Université, 2012-2013. Marion a été co-encadrée par Florence et moi-même et a participé à la caractérisation du modèle optogénétique. 2 • Dorian Chabbert : Master 2 Neurosciences Aix-Marseille Université, Spécialité : Neurobiologie, Neurophysiologie, Neuropathologie, 2012-2013. Dorian a repris la suite du travail de thèse de Delphine et a approfondi les relations entre les neurones striato-nigraux et les interneurones cholinergiques. Il a obtenu une bourse du ministère de l’Enseignement Supérieur et de la Recherche à l’issue de son master 2 et a poursuivi sa thèse dans le laboratoire sous la direction de P. Gubellini. • Gwenaëlle Laverne : Master 2 Biologie Santé, Sciences du médicament de l’Université de Poitiers, Spécialité : Recherche et Ingénierie et Bio-santé, 2015-2016. Gwenaëlle effectuait son Master à Poitiers et a voulu faire son stage dans le laboratoire pour se former aux techniques d’électrophysiologie et d’optogénétique. Elle a caractérisé le patron induit par l’activation de la channelrhodopsine sur l’activité électrique des interneurones cholinergiques. • Gwenaëlle Laverne : Thèse de doctorat Aix-Marseille Université, Spécialité : Neurosciences, 2016 - présent. Bien qu’ayant obtenu une bourse à l’université de Poitiers, Gwenaëlle a décidé de faire sa thèse avec moi sur les effets de la manipulation optogénétique des interneurones cholinergiques sur la plasticité cortico-striée à long terme. Elle est financée par un contrat que j’ai obtenu à la Fondation de France.
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