权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Projection-specific contributions of the ventromedial prefrontal cortex to fear extinction and fear generalization

腹内侧前额叶皮层对恐惧消退和恐惧泛化的投射特异性贡献

基本信息

批准号：
8982002
负责人：
Zachary Thomas Pennington
金额：
$ 3.44万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8982002
关键词：
Accounting Affect Affective Amygdaloid structure Anxiety Behavior Behavior Therapy Biological Biological Markers Brain region Cell Nucleus Chronic Development Disease Environment Excitotoxic lesion Experimental Designs Exposure to Extinction (Psychology)Foundations Freezing Fright Functional disorder Generations Individual Intercalated Cell Intervention Laboratories Lead Light Mediating Memory Modeling Neurons Output Pathway interactions Patients Pharmacological Treatment Play Post-Traumatic Stress Disorders Prefrontal Cortex Prevalence Prevention program Process Public Health Rattus Recruitment Activity Relative (related person)Resistance Risk Factors Rodent Rodent Model Role Stimulus Structure Structure of terminal stria nuclei of preoptic region Symptoms Synapses Syndrome Testing Thinking Time Trauma Treatment Efficacy United States Work base conditioned fear disorder prevention disorder risk experience fear memory insight learning extinction memory process new technology new therapeutic target novel novel strategies novel therapeutics public health relevance research study response stressor therapeutic target traumatic event vigilance

项目摘要

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) is a chronic, debilitating, syndrome, with an estimated lifetime prevalence of approximately 7% in the United States. Although there are affective behavioral and pharmacological treatments for PTSD, substantial gaps in treatment remain. The generation of novel treatment options is therefore paramount. Reduced activation of the ventromedial prefrontal cortex (vmPFC) has consistently been observed in PTSD patients, and may represent a biological target for treatment. However, just how alterations in vmPFC function contribute to PTSD symptomology, or how this region might be pharmacologically targeted, is presently unknown. Although previous findings suggest that this brain region is likely to be important for the reduction of fear responses to stimuli whe they are no longer predictive of threat (fear extinction), recent evidence suggests that the vmPFC may also play a role in reducing the generalization of fear states to situations in which a threat has not been experienced (fear generalization). The studies in this proposal seek to advance our understanding of how hypofunction of the vmPFC contributes to PTSD risk and symptomology, and provide novel insight into how deficits in fear extinction and fear generalization in PTSD might be generated by distinct downstream output structures of the vmPFC. Using a rodent model of PTSD, the proposed experiments will first determine the time points at which vmPFC hypoactivity are likely to contribute to symptoms. This will be done by comparing the effects of inactivating the vmPFC at the time of trauma, at the time of fear generalization, or at the time of fear extinction. This will help to identify when interventions directed at the vmPFC are likely to be beneficial. Furthermore, this work will be the foundation for studies aimed at understanding what other brain regions the vmPFC works in concert with in the modulation of fear responses. Second, using novel technology that allows specific connections between the vmPFC and selected brain regions to be inactivated, it will be determined whether different vmPFC connections play distinct roles in fear extinction and fear generalization. In particular, the hypothesis to be tested is that projections from the vmPFC to the intercalated cells of the amygdala mediate fear extinction, whereas projections from the vmPFC to the bed nucleus of the stria terminalis mediate fear generalization. By elucidating the direct mechanism by which the vmPFC interacts with other brain regions in PTSD-related behaviors, potentially novel therapeutic targets can be discovered.