Disentangling the Consequences of Trauma

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PROJECT SUMMARY/ABSTRACT Trauma impacts the life of nearly every individual and plays a pivotal role in shaping our mental health, leaving individuals vulnerable to an array of debilitating psychological conditions, including post-traumatic stress disorder, substance use disorders, anxiety, and depression. Much trauma research has focused on how memories for traumatic events are formed, with considerably less emphasis on the multifaceted processes contributing to these conditions. Further highlighting the importance of examining multiple trauma endpoints, growing evidence indicates that the consequences of trauma are behaviorally and biologically dissociable. Thus, the diverse pathological consequences of trauma may require individualized treatment targets. The experiments in this proposal will utilize a behavioral procedure that will allow the diverse consequences of trauma to be simultaneously studied in mice, combined with a sophisticated set of techniques for isolating biological variance, allowing for the disentanglement of their biological origins. Under the K99 portion of this proposal – to be completed at the Icahn School of Medicine at Mount Sinai under the mentorship of Drs. Denise Cai (primary mentor), Ian Maze (co-mentor), and Scott Russo (co-mentor) – I will first test the hypothesis that trauma induces lasting changes in amygdala trauma ensembles (i.e., neurons active in response to trauma) that results in enhanced responses to subsequent stressors, but not other anxiety-like phenotypes. This will be achieved using a combination of in vivo calcium imaging and selective optogenetic inhibition of trauma ensembles during subsequent behavioral tests. Further, I will use RNA sequencing of trauma ensembles to determine the transcriptional changes specific to these cells, in hopes of discovering novel targets for intervention. Technical training under the K99 portion will include optogenetics, fluorescence activated nuclear sorting, and transcriptomic analyses. Additionally, I will receive vital career development training on topics related to laboratory and personnel management, grant writing, communication/networking, and entering a tenure track position at a top-tier academic research institution. Under the R00 portion of this proposal, I will utilize a similar set of techniques to test the hypothesis that ventral hippocampal trauma ensembles support persistent anxiety-like behaviors after trauma. This work will provide both key insights into how trauma persistently influences anxiety-like behavior and robust preliminary data for my lab’s first grant applications. The training and support provided by this award will be instrumental as I establish a successful career focused on how trauma predisposes individuals to neuropsychiatric illness.