Distributed synaptic plasticity in fear conditioning

恐惧调节中的分布式突触可塑性

• 批准号: 7178523
• 负责人: FRED J HELMSTETTER
• 金额: $ 22.3万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-20 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7178523
• 关键词: Amygdaloid structure; Area; Auditory; Behavioral; Biological Models; Brain; Chromosome Pairing; Condition; Data; Disruption; Elements; Fright; Genetic Transcription; Geniculate body structure; Hippocampus (Brain); Injection of therapeutic agent; Laboratories; Lateral; Learning; Localized; Medial; Memory; Messenger RNA; Midbrain structure; Modification; Molecular; Neurons; Nuclear; Predisposition; Procedures; Process; Protein Biosynthesis; Proteins; Rattus; Relative (related person); Retrieval; Series; Site; Structure; Synapses; Synaptic plasticity; System; Testing; Thalamic structure; Time; Training; Translations; Work; conditioned fear; design; insight; long term memory; memory retrieval; midbrain central gray substance; neural circuit; research study

.DESCRIPTION (provided by applicant): Pavlovian fear conditioning in rats is a powerful model system currently being used to study memory at the molecular, cellular, and systems level. Recent work with this procedure indicates that the formation of long-term memory for fear conditioning requires the synthesis of new mRNA and protein in the amygdala and hippocampus. Furthermore, it appears that after these memories are retrieved from storage they go through a second time period during which protein synthesis is required. Our data indicate that while initial learning requires both mRNA and protein synthesis in amygdala neurons, the "stabilization" of memory after retrieval does not require mRNA transcription. This suggests that while initial memory formation requires nuclear transcription, the modification of synapses after retrieval may involve dendridic protein synthesis using local mRNA. We also provide evidence showing that mRNA and/or protein synthesis is required for new learning not only in the amygdala, but also in structures throughout the neural circuit active during fear conditioning. The experiments proposed here will evaluate the relative contribution of mRNA transcription and protein translation to memory consolidation and "reconsolidation" at multiple brain sites including the amygdala, hippocampus, medial geniculate nucleus of the thalamus, and periaqueductal gray region of the midbrain. We will describe the relative post-training time course of these processes at several sites and begin to explore specific functional contributions of each brain area to learning. The results will provide important new insights into the mechanisms of memory formation and long-term stability at the molecular and systems level.

．描述（由申请人提供）：大鼠的巴甫洛夫恐惧条件反射是一个强大的模型系统，目前被用于在分子、细胞和系统水平上研究记忆。最近对这一过程的研究表明，恐惧调节的长期记忆的形成需要杏仁核和海马体中新的mRNA和蛋白质的合成。此外，在这些记忆被从存储器中提取出来之后，它们似乎经历了需要蛋白质合成的第二段时间。我们的数据表明，虽然最初的学习需要杏仁核神经元的mRNA和蛋白质合成，但在检索后记忆的“稳定”不需要mRNA转录。这表明，虽然初始记忆的形成需要核转录，但检索后突触的修饰可能涉及使用局部mRNA合成树突蛋白。我们还提供证据表明，mRNA和/或蛋白质的合成不仅在杏仁核中需要，而且在整个神经回路的结构中也需要。