Project description DEENESFRITPL Neuronal mechanisms underlying traumatic memory attenuation Fear, anger, anxiety and depression or guilt are all common reactions to trauma. The distressing memory of a traumatic event may be mitigated, however, over time and through an adaptative psychological process. Yet a lack of therapeutic support often leads to severe trauma-related disorders. In this context, the EthoFearless project, funded by the European Research Council, will 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. The findings 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. Show the project objective Hide the project objective Objective 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. Keywords Fear extinction PTSD NeuroEthology Learning and Memory Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-STG - ERC STARTING GRANTS Call for proposal ERC-2021-STG See other projects for this call Funding Scheme HORIZON-ERC - Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 1 497 500,00 Address Rue michel ange 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Participants (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CONSIGLIO NAZIONALE DELLE RICERCHE Participation ended Italy Net EU contribution € 0,00 Address Piazzale aldo moro 7 00185 Roma See on map Region Centro (IT) Lazio Roma Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
