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Disentangling the Consequences of Trauma

理清创伤的后果

基本信息

批准号：
10571405
负责人：
Zachary Thomas Pennington
金额：
$ 12.61万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10571405
关键词：
Acute Affect Amygdaloid structure Animals Anxiety Applications Grants Auditory Award Behavior Behavioral Behavioral Assay Biological Brain Calcium Cells Communication Darkness Data Data Set Dedications Development Disease Event Fluorescence Fright Future Gene Expression Genes Genetic Transcription Goals Grant Health Hippocampus Image Individual Institution Intervention Laboratories Learning Life Light Measures Memory Mental Depression Mental Health Mental disorders Mentors Mentorship Modeling Molecular Molecular Profiling Monitor Mood Disorders Multiple Trauma Mus Neurons Nuclear Pathologic Personnel Management Phenotype Play Positioning Attribute Post-Traumatic Stress Disorders Procedures Process Protein Synthesis Induction Psyche structure Research Research Personnel Role Shapes Sorting Stimulus Stress Substance Use Disorder Synaptic Transmission Techniques Testing Time Training Trauma Trauma Research Vulnerable Populations Work Writing anxiety-like behavior behavior test biobehavior biological adaptation to stress career career development defined contribution differential expression experience experimental study gene network in vivo calcium imaging individualized medicine insight medical schools neural neuropsychiatry novel optogenetics post-trauma programs psychologic response stressor tenure track tool transcriptome sequencing transcriptomics traumatic event

项目摘要

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.

项目总结/文摘