Understanding whole-brain circuits mediating fear memory attenuation

ongoing

The experience of aversive events is a component of everyone’s lives. People perceive aversive events and traumas differently but the explanation of this different perception is poorly understood. At times, this different perception leads to chronic fear disorders like phobias and post-traumatic stress disorder (PTSD). Despite the high prevalence of such disorders, effective treatments for traumatic memories remain scarce. Therefore, a good understanding of the time-evolution of fear memory is necessary to clarify how different neuronal circuits are disrupted in disease states but also to set the basis for the development of unified therapeutic strategy to attenuate PTSD. Currently, the limited knowledge of the mechanisms underlying fear memory at brain-wide level is mainly due to the technical limitations in large-scale analysis of neuronal activity. TaggingMemory seeks to study the anatomical and functional circuitry underlying fear memory extinction reconstructing single-cell-resolution maps of whole-brain connectivity. The identification of this circuitry could pave the way for a better comprehension of PTSD circuitry at single-individual level. To reach this goal, I will develop a new quadruple transgenic mouse model able to capture multiple memories in the same brain. Using this transgenic line such as preclinical model of PTSD, I will reconstruct the evolutionary maps of fear memory. Then, I will test psychedelics as new promising drugs for PTSD treatment in order to analyze how fear attenuation changes with or without drug treatment, highlighting the connectivity differences that drive fear suppression. Finally, by identifying brain regions pivotal for a successful memory extinction, I will then unravel the anatomical circuits with sub-cellular resolution by a cutting-edge intelligent light-sheet microscope. The present action will pioneer the anatomical and functional characterization of the well-known but poorly understood phenomenon of fear memory.