Innovating Works

EthoFearless

Financiado
Attenuation of ethological traumatic memories
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 understan... 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. ver más
31/08/2028
CNRS
1M€
Perfil tecnológico estimado
Duración del proyecto: 70 meses Fecha Inicio: 2022-10-03
Fecha Fin: 2028-08-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-10-03
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2021-STG: ERC STARTING GRANTS
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5