CRF-R1 mediation of fear: a viral vector approach

CRF-R1 介导恐惧：病毒载体方法

• 批准号: 6750747
• 负责人: HEMANTH P NAIR
• 金额: $ 4.89万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750747
• 关键词: Lentivirus; amygdala; anxiety; corticotropin releasing factor; cyclic AMP; fear; immunocytochemistry; laboratory rat; neurotransmitter receptor; postdoctoral investigator; receptor expression; stress; thalamus; transfection /expression vector

DESCRIPTION (provided by applicant): Previous research has demonstrated that while conditioned fear may rely predominantly on the central nucleus of the amygdala (CEA), responses to less predictable or unconditioned anxiogenic stimuli, or fear states akin to anxiety may depend on the bed nucleus of the stria terminalis (BNST). Furthermore, this dissociation may be related to CRF type I (CRF-RI) receptor activity in the two regions. The major goal, and second specific aim of this proposal is to use a lentiviral vector to over-express the CRF-R1 receptor in the BNST or CEA of adult rats and assess its effects on different forms of facilitation of the acoustic startle reflex, a measure of fear. The hypothesis is that over-expression in the CEA will facilitate fear-potentiated startle; a form of conditioned fear, and over-expression in the BNST will facilitate baseline acoustic and light-enhanced startle, measures of general stress/anxiety and unconditioned fear, respectively. These studies assume that over-expression of a receptor is rate limiting. They also depend on a localized and sustained expression of the CRF-R1 transgene. Therefore, the first specific aim is to a) assess whether viral mediated increases in CRF-R1 receptors will change binding and cAMP levels in vitro, B) characterize in-vivo the spread of virus following injection and C) characterize the time course of expression. The proposed studies aim to contribute to our understanding of the neurological basis of anxiety disorders or disorders of fear (e.g. post-traumatic stress disorder).

描述（由申请人提供）：先前的研究表明，虽然条件性恐惧可能主要依赖于杏仁核中央核（CEA），但对难以预测或非条件性焦虑刺激的反应，或类似于焦虑的恐惧状态可能取决于床核终纹（BNST）。此外，这种解离可能与这两个区域的 CRF I 型 (CRF-RI) 受体活性有关。该提案的主要目标和第二个具体目标是使用慢病毒载体在成年大鼠的 BNST 或 CEA 中过度表达 CRF-R1 受体，并评估其对不同形式的声惊吓反射促进的影响。恐惧程度。假设 CEA 中的过度表达会促进恐惧增强的惊吓；一种条件性恐惧，以及 BNST 中的过度表达将分别促进基线声学和光增强惊吓、一般压力/焦虑和无条件恐惧的测量。这些研究假设受体的过度表达是速率限制的。它们还依赖于 CRF-R1 转基因的局部持续表达。因此，第一个具体目标是 a) 评估病毒介导的 CRF-R1 受体增加是否会改变体外结合和 cAMP 水平，B) 表征注射后病毒在体内的传播，C) 表征表达的时间过程。拟议的研究旨在帮助我们了解焦虑症或恐惧症（例如创伤后应激障碍）的神经学基础。