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Modulation of Hindbrain and Spinal Locomotor Circuits by Interoceptive Mechanosensory Neurons Mingyue Wu

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Modulation of Hindbrain and Spinal Locomotor Circuits by Interoceptive Mechanosensory Neurons Mingyue Wu Modulation of hindbrain and spinal locomotor circuits by interoceptive mechanosensory neurons Mingyue Wu To cite this version: Mingyue Wu. Modulation of hindbrain and spinal locomotor circuits by interoceptive mechanosen- sory neurons. Neurons and Cognition [q-bio.NC]. Sorbonne Université, 2020. English. NNT : 2020SORUS121. tel-03242875 HAL Id: tel-03242875 https://tel.archives-ouvertes.fr/tel-03242875 Submitted on 31 May 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. Sorbonne Université École doctorale Cerveau-Cognition-Comportement (ED 158) Institut du Cerveau (ICM) Laboratoire Signalisation Sensorielle Spinale Modulation of hindbrain and spinal locomotor circuits by spinal interoceptive mechanosensory neurons Par Ming-Yue Wu Thèse de doctorat de Sciences de la vie, spécialité Neurosciences Dirigée par Dr. Claire Wyart Présentée et soutenue publiquement le 29/06/2020 Devant un jury composé de : Dr. Sandrine Bertrand Chargée de Recherche Rapportrice Dr. Réjean Dubuc Professeur Rapporteur Dr. Pascal Legendre Directeur de Recherche Examinateur Dr. Volker Bormuth Maître de conférences Examinateur Dr. Julien Bouvier Chargé de Recherche Examinateur Dr. Claire Wyart Directrice de Recherche Directrice de thèse -I dedicate this thesis to all my mentors that supervised me and trained me to do good science. 2 Table of Contents Acknowledgements ........................................................................................................................ iii Résumé ............................................................................................................................................ v Abstract ......................................................................................................................................... vii Abbreviations ................................................................................................................................. ix Chapter 1: Introduction ............................................................................................................... 1 I. The neural circuits underlying locomotion .......................................................................... 3 1. Mesencephalic locomotor region.................................................................................. 3 2. Reticulospinal neurons in brainstem send descending command to spinal motor circuits ..................................................................................................................................... 4 3. Circuits underlying the central pattern generation in the spinal cord ......................... 13 4. Neuromodulators to induce and adapt the locomotor activity .................................... 22 5. Integration of posture and locomotion........................................................................ 23 6. C-start response: a behavioral paradigm to study locomotor kinematics and circuits in teleost .................................................................................................................................... 24 II. Sensorimotor integration ................................................................................................ 28 1. Sensory afferents through DRG neurons .................................................................... 29 2. Proprioceptive pathways in anamniotes ..................................................................... 35 3. Deciphering the function of sensory feedback during active locomotion: combing genetic manipulation and optical approaches ....................................................................... 36 III. Intraspinal mechanosensory neurons contacting the CSF .............................................. 38 1. Morphology and development of CSF-cNs ................................................................ 38 2. Sensory modalities of CSF-cNs .................................................................................. 40 3. Modulation of locomotor behavior by CSF-cNs ........................................................ 41 4. Heterogeneity of CSF-cNs .......................................................................................... 41 IV. Aims of the thesis ........................................................................................................... 43 Chapter 2: Materials and Methods ........................................................................................... 45 I. Experimental model and subject details ............................................................................ 45 II. Living imaging and anatomy analysis ............................................................................ 46 III. Optogenetic assisted electrophysiology in vivo ............................................................. 46 IV. Two-photon mediated cell ablation ................................................................................ 49 i V. Behavior test and analysis .............................................................................................. 50 VI. Quantification and statistical analysis ............................................................................ 51 Chapter 3: Results....................................................................................................................... 54 I. Investigating the function of rostralmost CSF-cNs projecting from spinal cord to hindbrain ................................................................................................................................... 54 II. Investigating the projectome of CSF-cNs in spinal cord ............................................... 91 1. Spinal CSF-cNs form putative axo-axonic connections with excitatory premotor interneurons........................................................................................................................... 91 2. CSF-cNs form putative axo-axonic connections with spinal serotonergic neurons ... 96 Chapter 4: Discussion and perspectives .................................................................................... 98 I. Functions of CSF-cN projection onto hindbrain circuits ................................................... 98 1. CSF-cNs may gate descending command of RSNs to modulate escape behavior ..... 98 2. Experimental strategy to probe the modulation of other RSN output by CSF-cNs . 102 3. CSF-cNs may modulate descending neuromodulatory system ................................ 103 4. CSF-cNs may control active posture and gait transition by innervating Oc/Pec motoneurons ........................................................................................................................ 103 5. CSF-cNs may modulate the mouth movements ....................................................... 104 6. Rostralmost CSF-cNs should mainly exert modulation onto the hindbrain circuits 105 II. Further Investigation of CSF-cN Projection onto Spinal Circuits ............................... 105 1. CSF-cNs may modulate the activity of V2a interneurons ........................................ 105 2. CSF-cNs may modulate the rhythmogenesis via V3 interneurons ........................... 106 3. CSF-cNs may modulate spinal serotonergic neuronal activity ................................ 107 4. Periphery excitatory and intraspinal inhibitory sensory neurons cooperate to control active locomotion? .............................................................................................................. 108 III. Conclusion .................................................................................................................... 108 Reference ................................................................................................................................... 109 ii Acknowledgements This is the end of my PhD, a fantastic journey in science and an important experience that equipped my mind to start my career and future life. A lot of people in and out of the lab provided help and support during my 4.5 years staying in Paris. I would like to thank you all. First of all, I would thank my supervisor Claire for accepting me as a student in the lab and instructing me throughout the PhD project. Thank you for encouraging and inspiring me when I was almost lost in the endless cell recording, for your patience in training me to be rigorous and critical in research and scientific writing, for caring about my life in Paris because I’m long apart from my family. Your sense of responsibility for the lab and the society is so impressive and makes me realize that we can and we should be involved in making a better world. I would like to thank all the lab members including those already left the lab. I would thank Jeff for training me of experiments with zebrafish larva during my rotation in the lab, Kevin for training me of whole-cell patch recording when I started my project, Andy for troubleshooting in coding and behavioral experiments, Urs and Jenna for providing experience in ENP program and French administration, Lydia for shooting many
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