ODORgram · Dissecting olfactory engrams to predict and treat traumatic memories

Remembering fearful episodes is crucial for anticipating future threats. To this aim, some memories undergo consolidation, a process that selects and integrates important information into the existing knowledge base of the brain. Memory information is stored in specific subsets of neurons called engrams. As time elapses, memories undergo generalization, a useful process allowing related information to be incorporated into the original trace. However, excessive generalization becomes maladaptive when memory recall aberrantly occurs in conditions not related to the original event such as in Postraumatic Stress Disorder. Understanding how memories are generalized is of paramount importance for preventing and treating memory overgeneralization. Why do some fear memories degenerate into pathology? Can we predict which memories will overgeneralize? Can overgeneralization be corrected? Here, we aimed to use the mouse olfactory system to investigate the evolution of fear memory engrams. Indeed, the olfactory system offers a unique setting for the longitudinal observation and manipulation of memory engrams, as odors are processed by conserved neuronal maps in the olfactory bulbs. First, using calcium imaging visualization of individual divergence from the known common odor engram, we aim to define a cell code that can predict overgeneralization and, subsequently, the individual development of pathological memories. Furthermore, using a novel technique, FLiCRE, that allows permanent engram tagging at an unprecedented temporal precision, we aim to target odor-related fear memory engrams, and rectify overgeneralization by disassociating the neuronal engram of the traumatic experience from unrelated information. This proposal will uniquely dissect how memories are encoded in the olfactory system and provide a tool for understanding, predicting and improving traumatic memories.