Descripción del proyecto
Mecanismos neuronales subyacentes a la atenuación de la memoria traumática
El miedo, la ira, la ansiedad y la depresión o el sentimiento de culpa son reacciones frecuentes ante el trauma. Sin embargo, el recuerdo angustioso de un acontecimiento traumático puede mitigarse con el tiempo y mediante un proceso psicológico adaptativo. Aun así, la falta de apoyo terapéutico desemboca a menudo en graves trastornos relacionados con el trauma. En este contexto, el equipo del proyecto EthoFearless, financiado por el Consejo Europeo de Investigación, investigará (por primera vez) los circuitos neuronales subyacentes a la extinción de recuerdos traumáticos inducida por la exposición a amenazas naturalistas, a saber, depredadores y congéneres agresivos. Los hallazgos allanarán el camino hacia la identificación de nuevas dianas terapéuticas para trastornos relacionados con traumas y arrojarán luz sobre cómo el cerebro puede actualizar recuerdos complejos de manera flexible.
Objetivo
Traumatic experiences generate among the strongest memories that can result in trauma-related disorders. Despite the high prevalence of these disorders, effective treatment options are scarce, calling for a deterministic understanding of the neuronal mechanisms underlying traumatic memory attenuation. For this, rodent studies classically use fear extinction paradigms where aversive experiences are modeled with the exposure to an electrical foot shock. However, the simple nature of this stimulus does not mirror the complexity of traumatic events in humans which is likely to be processed by equally complex networks. Here, I propose to investigate for the first time the neural circuits underlying the extinction of traumatic memories induced by exposure to naturalistic threats, namely, predators and aggressive conspecifics. First, we will compile a comprehensive atlas of brain activity underlying extinction of these ethological traumas and generate network organization models, which will be causally probed by pathway-specific chemogenetic manipulations. Second, we will characterize the functional input-output connectome of ethological extinction centers using a combination of viral tracing, neuronal activity and optogenetically assisted circuit mapping. This set of data will, third, provide the substrate for the study of the neurophysiological and molecular mechanisms underlying efficient extinction of ethological traumas, which will be analyzed by pathway-specific in-vivo Ca2+ imaging, closed-loop optogenetics, ex-vivo electrophysiology and RNA sequencing. Lastly, we will investigate whether impairments at the level of these newly identified networks underlie extinction deficits at the basis of trauma-related disorders. Together, these results will pave the way for the identification of novel therapeutical targets for trauma-related disorders and shed light on how the brain can flexibly update complex memories.
Ámbito científico
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