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Muscarinic, Adenosine and Tropomyosin-Related Kinase B Receptor Modulate the Neuromuscular Developmental Synapse Elimination Process

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Muscarinic, Adenosine and Tropomyosin-Related Kinase B Receptor Modulate the Neuromuscular Developmental Synapse Elimination Process Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. 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UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà Laura Nadal Magriñà Muscarinic, adenosine and tropomyosin-related kinase B receptors modulate the neuromuscular developmental synapse elimination process DOCTORAL THESIS Thesis supervisors: Dr. Neus Garcia Dr. María Ángel Lanuza Prof. Josep Maria Tomàs Unitat d’Histologia i Neurobiologia Departament de Ciències Mèdiques Bàsiques UNIVERSITAT ROVIRA I VIRGILI Reus 2017 UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà UNITAT D’HISTOLOGIA I NEUROBIOLOGIA DEPARTAMENT DE CIÈNCIES MÈDIQUES BÀSIQUES FACULTAT DE MEDICINA I CIÈNCIES DE LA SALUT Neus Garcia Sancho, professora titular del Departament de Ciències Mèdiques Bàsiques de la Universitat Rovira i Virgili. María Ángel Lanuza Escolano, professora titular del Departament de Ciències Mèdiques Bàsiques de la Universitat Rovira i Virgili. Josep Maria Tomàs Ferré, catedràtic del Departament de Ciències Mèdiques Bàsiques de la Universitat Rovira i Virgili. FAIG CONSTAR que aquest treball, titulat ‘Muscarinic, adenosine and tropomyosin-related kinase B receptors modulate the neuromuscular developmental synapse elimination process’, que presenta Laura Nadal Magriñà per a l’obtenció del títol de Doctor, ha estat realitzat sota la meva direcció al Departament de Ciències Mèdiques Bàsiques d’aquesta Universitat i que acompleix els requeriments per poder optar a Menció Internacional. Reus, 27 de març de 2017 La directora i els codirectors de la tesi doctoral, Dr. Neus Garcia Sancho Dr. María Ángel Lanuza Escolano Prof. Josep Maria Tomàs Ferré UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà “Learn from yesterday, live for today, hope for tomorrow. The important thing is to not stop questioning”. Albert Einstein UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà i. INDEX OF FIGURES ...................................................................................................... i INDEX ii. INDEX OF TABLES ........................................................................................................ v iii. ABBREVIATIONS ........................................................................................................ vii ABSTRACT ....................................................................................................................... xi I. INTRODUCTION ........................................................................................................... 1 1. THE NEUROMUSCULAR JUNCTION: STRUCTURE, FUNCTION AND DEVELOPMENT ......................................................................................................... 1 1.1. Structure of neuromuscular junction ......................................................... 2 1.1.1. Presynaptic component........................................................................ 3 1.1.2. Synaptic cleft and basement membrane ........................................... 5 1.1.3. Postsynaptic component ...................................................................... 6 1.1.4. Glial component .................................................................................... 7 1.2. Function of neuromuscular junction.......................................................... 9 1.2.1. Neuromuscular transmission .................................................................. 9 1.3. Development in neuromuscular junction ............................................... 11 1.3.1. Embryonic stage .................................................................................. 12 1.3.2. Postnatal stage .................................................................................... 14 2. SYNAPSE ELIMINATION PROCESS...................................................................... 16 2.1. Presynaptic component: from poly- to mononeuronal muscle fiber innervation .......................................................................................................... 16 2.2. Postsynaptic component .......................................................................... 20 2.3. Glial component......................................................................................... 22 2.4. Molecules involved in synaptic elimination process ............................ 23 2.5. Synaptic activity ......................................................................................... 28 3. MUSCARINIC, ADENOSINE AND NEUROTROPHIN RECEPTORS IN SYNAPTIC ELIMINATION PROCESS .......................................................................................... 31 3.1. Muscarinic receptors.................................................................................. 31 3.1.1. mAChRs in the NMJ ............................................................................. 32 3.1.2. mAChRs and synapse elimination ...................................................... 33 3.1.3. Muscarinic agonists and antagonists ................................................. 33 3.1.3.1. Muscarinic agonists ............................................................... 33 3.1.3.2. Muscarinic antagonists ......................................................... 34 3.2. Adenosine receptors.................................................................................. 36 UNIVERSITAT ROVIRA I VIRGILI Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà 3.2.1. ARs in the NMJ ......................................................................................38
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