Synaptic tagging in the lateral amygdala fear conditioning circuit

外侧杏仁核恐惧调节回路中的突触标记

• 批准号: 7927173
• 负责人: LINNAEA E OSTROFF
• 金额: $ 5.58万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7927173
• 关键词: Address; Amygdaloid structure; Animal Experiments; Animals; Anisomycin; Area; Auditory; Cannulas; Cells; Conditioned Stimulus; Contralateral; Cyclic AMP-Dependent Protein Kinases; Data; Dependence; Disease; Electric Stimulation; Electrodes; Electron Microscopy; Frequencies; Fright; Geniculate body structure; Hippocampus (Brain); Hour; Implant; Individual; Injection of therapeutic agent; Intralaminar Nuclear Group; Ipsilateral; Lateral; Learning; Long-Term Potentiation; Maintenance; Medial; Memory; Mental disorders; Modeling; Pain; Pathway interactions; Phobic anxiety disorder; Plastics; Process; Production; Protein Biosynthesis; Protein Synthesis Inhibition; Protein Synthesis Inhibitors; Proteins; Protocols documentation; Rattus; Recruitment Activity; Relative (related person); Role; Short-Term Memory; Signal Transduction; Stimulus; Synapses; Synaptic plasticity; Testing; Thalamic structure; Time; Tracer; Training; Translations; base; conditioned fear; conditioning; long term memory; prevent; response; therapy development; transmission process

DESCRIPTION (provided by applicant): Auditory fear conditioning, a learning paradigm in which a rat can form an association between a previously neutral tone and a painful stimulus, is believed to occur via the persistent strengthening of synaptic connections, termed long-term potentiation (LTP), in the lateral amygdala (LA). Protein synthesis is necessary for both consolidation and reconsolidation of fear conditioning memory, and this may suggest a role for synapse remodeling. Auditory information enters the LA via plastic synapses from both the thalamus and cortex, but the functional and anatomical relationship between these synapses is unclear. The proposed project will begin to investigate the relative roles of these synapses in fear conditioning memory and their structural underpinnings. First, the protein synthesis-dependence of LTP consolidation and reconsolidation will be compared between the cortical and thalamic input pathways using a behaviorally relevant induction protocol. Second, serial section electron microscopy will be used to examine ultrastructural changes in LA synapses that occur during consolidation of fear conditioning and LTP, including changes in synapse size, synapse number, and local protein synthesis. Tracer injections will allow comparison of cortical and thalamic synapses under all conditions. A better understanding of the synaptic basis of the formation and maintenance of fear memories is important for the development of interventions for psychiatric disorders involving fear associations, such as phobias.

描述（由申请人提供）：听觉恐惧条件反射是一种学习范式，其中大鼠可以在先前的中性音调和疼痛刺激之间形成关联，据信通过持续加强外侧杏仁核（LA）中的突触连接（称为长时程增强（LTP））来发生。蛋白质合成对于恐惧调节记忆的巩固和重新巩固都是必要的，这可能表明突触重塑的作用。听觉信息通过丘脑和皮层的塑料突触进入 LA，但这些突触之间的功能和解剖关系尚不清楚。拟议的项目将开始研究这些突触在恐惧调节记忆中的相对作用及其结构基础。首先，将使用行为相关的诱导方案在皮质和丘脑输入通路之间比较 LTP 巩固和再巩固的蛋白质合成依赖性。其次，连续切片电子显微镜将用于检查在恐惧调节和 LTP 巩固过程中发生的 LA 突触超微结构变化，包括突触大小、突触数量和局部蛋白质合成的变化。示踪剂注射将允许在所有条件下比较皮质和丘脑突触。更好地了解恐惧记忆形成和维持的突触基础对于制定针对涉及恐惧关联的精神疾病（例如恐惧症）的干预措施非常重要。