Molecular signaling underlying trace fear conditioning in hippocampus and mPFC

海马和 mPFC 中微量恐惧调节的分子信号传导

• 批准号: 7615358
• 负责人: MARIEKE R GILMARTIN
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615358
• 关键词: Affect; Amygdaloid structure; Anxiety; Behavior; Cognitive; Confocal Microscopy; Decision Making; Dendrites; Episodic memory; Fright; Hippocampus (Brain); Human; Immunofluorescence Immunologic; Infusion procedures; Learning; MAP Kinase Gene; MAPK Signaling Pathway Pathway; Medial; Mediating; Memory; Molecular; Neurons; Numbers; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Proteins; Research; Signal Transduction; Signaling Protein; Structure; System; Testing; Translations; Western Blotting; Work; clinically relevant; conditioned fear; experience; human FRAP1 protein; inhibitor/antagonist; insight; intracellular protein transport; long term memory; neuronal cell body; protein localization location; relating to nervous system; research study

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to determine how the hippocampus, medial prefrontal cortex (mPFC), and amygdala interact at the systems, cellular, and molecular levels to support the formation of long-term memory. The experiments in this project use a hippocampus-dependent task called trace fear conditioning (TFC), which has a temporal component for which the mPFC may be important. The findings from my doctoral work, which recorded single neurons in the hippocampus and mPFC during TFC, suggest that these structures work together to form trace fear memories (Gilmartin & McEchron, 2005 a,b), but a functional interaction has not been tested. Specific Aim 1 will directly test for a hippocampal-prefrontal interaction during TFC. This aim will combine pharmacological inactivation of the hippocampus with protein immunostaining in the mPFC to determine whether hippocampal activity is necessary for plasticity-related signaling mechanisms in the mPFC. Aim 1 will also include the amygdala. Aim 2 will use targeted infusions of a selective protein translation inhibitor to examine the contribution of translations! mechanisms to trace fear memory formation. Aim 3 will provide new information about whether plasticity-related signaling and protein translation are mediated by a common signaling mechanism during TFC. In addition to western-blot analysis, several experiments will also use immunofluorescence and confocal microscopy to examine differences in protein localization (e.g. prelimbic vs. infralimbic mPFC; dendrites vs. soma). The results of this project will provide new insights into hippocampal-prefrontal function, applicable to several clinically relevant issues. The hippocampus is important for declarative and episodic memories, and the mPFC is implicated in higher-order processes such as decision-making and situation-appropriate behavior. As learned experiences influence our decisions and guide our actions, an interaction between hippocampal and prefrontal networks is critical to a number of different cognitive processes. The results of this proposal will have the potential to guide further research into how these two structures work together during normal as well as aberrant neural processes that affect a significant subset of the human population, such as anxiety and post-traumatic stress disorders.

描述（由申请人提供）：本提案的长期目标是确定海马体、内侧前额叶皮质（mPFC）和杏仁核如何在系统、细胞和分子水平上相互作用，以支持长期记忆的形成。在这个项目中的实验使用了一个依赖于校园的任务，称为跟踪恐惧条件反射（TFC），其中有一个时间的组成部分，mPFC可能是重要的。我的博士研究记录了TFC期间海马体和mPFC中的单个神经元，结果表明这些结构共同作用形成了微量恐惧记忆（Gilmartin & McEchron，2005 a，B），但功能性相互作用尚未得到测试。具体目标1将直接测试在TFC期间的前额叶-前额叶相互作用。该目标将结合联合收割机的药理学失活的海马与蛋白质免疫染色的mPFC，以确定是否海马活动是必要的可塑性相关的信号机制，在mPFC。目标1还包括杏仁核。目标2将使用选择性蛋白质翻译抑制剂的靶向输注来检查翻译的贡献！追踪恐惧记忆形成的机制目的3将提供新的信息是否可塑性相关的信号和蛋白质翻译介导的共同信号机制在TFC。除了蛋白质印迹分析，几个实验还将使用免疫荧光和共聚焦显微镜检查蛋白质定位的差异（例如，边缘前与边缘下mPFC;树突与索马）。该项目的结果将提供新的见解，适用于几个临床相关问题的前额叶功能。海马体对陈述性记忆和情景记忆很重要，mPFC涉及更高阶的过程，如决策和情境适当的行为。由于学习经验影响我们的决定并指导我们的行动，海马和前额叶网络之间的相互作用对许多不同的认知过程至关重要。这项提议的结果将有可能指导进一步研究这两种结构如何在正常和异常的神经过程中共同工作，这些神经过程影响了人类人口的一个重要子集，如焦虑和创伤后应激障碍。