Modulation of Fear Memory by Corticotropin-Releasing Factor in the Amygdala

杏仁核促肾上腺皮质激素释放因子对恐惧记忆的调节

基本信息

批准号：
8180373
负责人：
ELIZABETH P BAUER
金额：
$ 39.24万
依托单位：
BARNARD COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8180373
关键词：
Affect Amygdaloid structure Animals Anxiety Anxiety Disorders Arts Auditory Award Behavior Behavioral Bilateral Biological Sciences Brain CRF receptor type 1 Calcium-Binding Proteins Cannulas Cell Nucleus Cells Clinical Trials Confocal Microscopy Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Receptors Data Development Educational process of instructing Electrophysiology (science)Elements Exhibits Extinction (Psychology)Fluorescence Microscopy Foundations Fright Green Fluorescent Proteins Implant In Vitro Individual Infusion procedures Interneurons Learning Long-Term Potentiation Memory Methods Molecular Neurons Neuropeptides Pharmacologic Substance Property Research Personnel Role Staining method Stains Stress Students Synapses Synaptic Transmission Synaptic plasticity System Techniques Thalamic structure Training Transgenic Organisms Woman Work base career clinically relevant college conditioned fear excitatory neuron human subject inhibitory neuron insight learning extinction long term memory receptor relating to nervous system research study response skills

项目摘要

DESCRIPTION (provided by applicant): There is a growing realization that human subjects with anxiety disorders exhibit abnormalities in how they acquire and/or extinguish conditioned fear responses. Thus, understanding how anxiety and conditioned fear interact at the neuronal level has direct clinical relevance. The neuropeptide corticotropin-releasing factor (CRF) is released throughout the brain under conditions of stress and anxiety. The amygdala contains particularly dense concentrations of CRF receptors whose activation leads to anxious behaviors. Yet the modulation of fear learning by this neuropeptide and indeed the interaction between anxiety and fear learning has not been comprehensively explored. We propose to examine this question by using multiple complementary methods. We will first analyze the anatomical distribution of CRF receptors within the basolateral nucleus of the amygdala (BLA), determining whether these receptors are located on the principal excitatory neurons of the BLA and/or on subsets of inhibitory interneurons. We will next examine behaviorally how CRF modulates fear learning and expression. Finally, using in vitro electrophysiology, we will study how CRF affects electrophysiological properties of BLA neurons and synaptic plasticity. Together, the experiments in this proposal represent an important step in understanding how CRF modulates Pavlovian fear conditioning. Thus, the results of this project may yield fundamental insights into the causes of anxiety disorders and provide a foundation for clinical investigation and pharmaceutical development. PUBLIC HEALTH RELEVANCE: Many anxiety disorders can be characterized by abnormalities in acquiring or extinguishing conditioned fear. This project will explore the relationship between a key neuropeptide associated with anxiety and the ability to learn and express conditioned fear responses.

描述（由申请人提供）：越来越意识到，患有焦虑症的人类受试者在获取和/或扑灭条件的恐惧反应方面表现出异常。因此，了解焦虑和条件恐惧如何在神经元水平上相互作用具有直接的临床相关性。在压力和焦虑的条件下，整个大脑释放了神经肽皮质激素释放因子（CRF）。杏仁核包含特别浓度的CRF受体，其激活会导致焦虑行为。然而，尚未全面探索这种神经肽对恐惧学习的调节，甚至焦虑与恐惧学习之间的相互作用尚未得到全面探索。我们建议通过使用多种互补方法来检查这个问题。我们将首先分析杏仁核（BLA）基底外侧核中CRF受体的解剖学分布，以确定这些受体是否位于BLA的主要兴奋性神经元和/或抑制性中间神经元子集中。接下来，我们将在行为上研究CRF如何调节恐惧学习和表达。最后，使用体外电生理学，我们将研究CRF如何影响BLA神经元和突触可塑性的电生理特性。同时，该提案中的实验代表了了解CRF如何调节Pavlovian恐惧条件的重要步骤。因此，该项目的结果可能会产生对焦虑症原因的基本见解，并为临床研究和药物开发提供基础。公共卫生相关性：许多焦虑症的特征是获得或消除条件恐惧的异常。该项目将探讨与焦虑相关的关键神经肽与学习和表达有条件恐惧反应的能力之间的关系。