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Authors & Affiliations
Alessandra Franceschini, Alessia Mastrodonato, Gergely Turi, Christine Ann Denny
Abstract
The experience of aversive events is a component of everyone’s lives. People perceive aversive events and traumas in distinct ways, but the explanation of this different perception is poorly understood. In some cases, maladaptive responses to traumatic events may leads to chronic fear disorders, including post-traumatic stress disorder (PTSD). Despite the high prevalence of such disorders, effective treatments for trauma remain scarce. Recently, psilocybin has emerged as a promising drug for major depressive disorder (MDD) and potentially PTSD. However, its mechanism of action and how it could potentially alter trauma (e.g., fear memories) remains to be characterized. Here, we utilized a novel, genetic system that allows for the tagging of multiple Arc ensembles in the same mouse in order to understand: 1) the evolution of trauma (e.g., fear memories), and 2) how pharmacological manipulation of individual fear memories produces improved behavior. This new tagging system called the mArc system allows for the labeling of three different ensembles (e.g., fear encoding, fear extinction, and spontaneous recall) in the same mouse. Using this system, we will identify these fear ensembles in brain regions classically involved in fear memory such as the dentate gyrus, CA3, anterior cingulate cortex, and basolateral amygdala. In summary, our innovative multiple Arc tagging system will allow to investigate how fear circuits are modified in mice treated by the drug and to quantitatively characterize the neuronal pathways involved in the time-evolution of fear memory.