Etude des circuits Ascendants et descendants et leur influence sur la transmission des signaux sensoriels dans le moelle épinière

par Noemie Frezel

Projet de thèse en Neurosciences

Sous la direction de Christian Specht.

Thèses en préparation à Paris Sciences et Lettres en cotutelle avec l'Université de Zurich , dans le cadre de École doctorale Cerveau, cognition, comportement (Paris) , en partenariat avec Institut de Biologie de l'École Normale Supérieure (laboratoire) et de École normale supérieure (Paris ; 1985-....) (établissement de préparation de la thèse) depuis le 01-10-2015 .


  • Résumé

    Noxious stimuli are sensed by specialized nociceptors of the peripheral nervous system. The information is then integrated in the spinal cord dorsal horn, which contains many interneurons and projection neurons sending axons to the brain. Excitatory and Inhibitory interneurons are part of complex circuits that process, integrate and relay different submodalities of sensory and painful information. Additionnally, supraspinal structures in the brain send axons to the spinal cord that contribute to gating and integration of the information coming in from the periphery. In many pathologies this transmission can be altered, leading to hyperalgesia and allodynia. We have identified a population of pyramidal neurons in the sensory cortex that projets directly to the dorsal horn of the spinal cord. In order to identify the connectivity and specific role of these neurons, we use genetically modified mice expressing recombinases (CRE and/or DRE) under the control of subtype-specific promoters. In combination with the use of reporter lines and recombination-dependent viruses, these mice allow identification, manipulation, and tracing of neurons and circuits involved in pain processing. In particular, we use adeno-associated viruses (AAVs) encoding DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to activate or silence neurons, or bacterial toxins to ablate specific populations. We also use AAVs encoding fluorescent proteins or the neuronal anterograde tracer WGA, as well as retrograde tracing rabies viruses for morphological and circuit analysis. Our goal is to apply these tools to identify the synaptic connections between supraspinal neurons and spinal cord interneurons. More preciselly, the injection of CRE-dependant AAVs encoding fluorescent proteins has lead us to identify direct projections from the sensory cortex to the spinal cord in mice expressing the CRE recombinase under the CCK promoter. We will use DREADD encoding viruses to study the function of these neurons and their influence on sensory processing. This will lead to greater insight on how peripheral sensory information is gated and processed in the dorsal horn and the brain. Neurochemical, morphological and functional analysis of dorsal horn circuitry, together with behavioral examination of the mice will allow to decipher neuronal players of pain processing and mechanisms of hypersensitivity.

  • Titre traduit

    Tools to study acsending and descending pathways and their influence on spinal sensory processing


  • Résumé

    Noxious stimuli are sensed by specialized nociceptors of the peripheral nervous system. The information is then integrated in the spinal cord dorsal horn, which contains many interneurons and projection neurons sending axons to the brain. Excitatory and Inhibitory interneurons are part of complex circuits that process, integrate and relay different submodalities of sensory and painful information. Additionnally, supraspinal structures in the brain send axons to the spinal cord that contribute to gating and integration of the information coming in from the periphery. In many pathologies this transmission can be altered, leading to hyperalgesia and allodynia. We have identified a population of pyramidal neurons in the sensory cortex that projets directly to the dorsal horn of the spinal cord. In order to identify the connectivity and specific role of these neurons, we use genetically modified mice expressing recombinases (CRE and/or DRE) under the control of subtype-specific promoters. In combination with the use of reporter lines and recombination-dependent viruses, these mice allow identification, manipulation, and tracing of neurons and circuits involved in pain processing. In particular, we use adeno-associated viruses (AAVs) encoding DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to activate or silence neurons, or bacterial toxins to ablate specific populations. We also use AAVs encoding fluorescent proteins or the neuronal anterograde tracer WGA, as well as retrograde tracing rabies viruses for morphological and circuit analysis. Our goal is to apply these tools to identify the synaptic connections between supraspinal neurons and spinal cord interneurons. More preciselly, the injection of CRE-dependant AAVs encoding fluorescent proteins has lead us to identify direct projections from the sensory cortex to the spinal cord in mice expressing the CRE recombinase under the CCK promoter. We will use DREADD encoding viruses to study the function of these neurons and their influence on sensory processing. This will lead to greater insight on how peripheral sensory information is gated and processed in the dorsal horn and the brain. Neurochemical, morphological and functional analysis of dorsal horn circuitry, together with behavioral examination of the mice will allow to decipher neuronal players of pain processing and mechanisms of hypersensitivity.