Descripción del proyecto
Estudio multiómico de las neuronas reticuloespinales
Todos los movimientos vitales son el resultado de una estrecha, aunque poco estudiada, cooperación entre el encéfalo y la columna vertebral. El equipo del proyecto ReticulOme, financiado por el Consejo Europeo de Investigación, pretende centrarse en los protagonistas de este proceso: las neuronas reticuloespinales (RS). Estas son sorprendentemente diversas, lo que implica que podrían interactuar con diferentes tipos de células y tener distintos antecedentes genéticos. Poco se sabe de su organización y de cómo da lugar a los movimientos compuestos que observamos. El equipo del proyecto empleará la multiómica en diferentes subconjuntos de neuronas RS en ratones. En ReticulOme se espera desvelar la complejidad de la coordinación neuronal que subyace al movimiento, mediante el estudio de los genes que se expresan en las células antes y después de la señal motora, así como las interacciones entre estas células.
Objetivo
The execution of coordinated and adaptive movements is the final manifestation of virtually all brain processes. Altered motor function is hence an associate feature of almost all conditions that affect the nervous system and is highly debilitating. This program will shed new light on the neuronal basis of movements with a focus on the cooperative roles of the brain and the spinal cord for composing and orchestrating multifaceted and adaptive motor behaviors.
Reticulospinal (RS) neurons of the brainstem reticular formation (RF) are pivotal for controlling the most vital movements. They have long been seen as a unified relay of command signals from various integrative centers upstream, to most, if not all, executory motor circuits downstream. Yet, based on recent findings and our ongoing work, we posit that RS neurons rather exhibit a substantial diversity and specialization by inputs and outputs that may support a form of selection and mixing of unitary components of composite motor behaviors.
Imprinting from the advent of multi-omics strategies in the mouse model, we will intersect functional connectomics and single-cell gene expression (the transcriptome) to achieve a most comprehensive characterization of RS neurons diversity, specialization, and interactions with their upstream and downstream brain areas. We will first investigate the anatomo-functional organization of an already circumscribed subset of RS neurons for orchestrating orienting motor actions. We will in parallel investigate the role and connectivity of other RS neurons, and provide genetic hallmarks of new functionally-relevant subsets. Our results will propel forward our understanding of the complex organization of the RF, its role in orchestrating composite movements, and its links with the rest of the brain. They will also provide new genetic hallmarks of RS neurons diversity which will be precious handles to ultimately examine and act on specific cell types in post-traumatic contexts.
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
75794 Paris
Francia