The Role of Neuronal Ensembles Supporting Auditory Fear Conditioning (Engrams) in the Amygdala in Memory Formation, Generalization and Extinction

杏仁核中支持听觉恐惧调节（印迹）的神经元群在记忆形成、泛化和消退中的作用

• 批准号: 10087966
• 负责人: Sheena A Josselyn
• 金额: $ 33.78万
• 依托单位: HOSPITAL FOR SICK CHLDRN (TORONTO)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10087966
• 关键词: Address; Amygdaloid structure; Anxiety; Anxiety Disorders; Architecture; Auditory; Behavior; Brain; Calcium; Cell Nucleus; Cells; Code; Dangerousness; Data; Development; Disease; Endoscopes; Event; Extinction (Psychology); Fluorescent in Situ Hybridization; Freezing; Fright; Future; Halorhodopsins; Hippocampus (Brain); Image; Immediate-Early Genes; Lateral; Lead; Light; Maps; Mediating; Memory; Mental disorders; Messenger RNA; Microscopy; Mus; Neurons; Nuclear; Opsin; Population; Post-Traumatic Stress Disorders; Prevention strategy; Process; Recurrence; Research Personnel; Retrieval; Role; Stimulus; System; Techniques; Testing; Time; Tissues; Training; Training Activity; Virus; Wild Type Mouse; base; conditioned fear; data analysis pipeline; effective therapy; experience; fear memory; graph theory; in vivo calcium imaging; innovation; machine learning algorithm; memory consolidation; neuronal excitability; optogenetics; promoter; recruit; therapy development; treatment strategy

Project Summary/Abstract Memory may be defined as the retention over time of internal representations gained through experience, and the capacity to reconstruct these representations at later times (Dudai 2007). These internal representations are thought to be encoded by long-lasting physical brain changes (memory traces or `engrams') (Josselyn, Kohler & Frankland 2015, 2017; Tonegawa et al. 2015; Schacter 2001). Remembering fear-evoking events is adaptive; it helps one make future choices based on past experience. It may even be beneficial to generalize some fearful memories. However, excessive fear generalization or treating no-longer threatening stimuli as dangerous may be maladaptive. Indeed, recurrent or inappropriately expressed fearful memories are a major component of several psychiatric diseases, including post-traumatic stress disorder (PTSD) and anxiety. Therefore, understanding how memory traces for fearful events are formed, change over time, under what conditions they remain specific or generalize, and how they are impacted by behavioral extinction are critical questions to not only understanding how the brain uses information but also for informing the development of new treatment/prevention strategies for disorders characterized by inappropriate fear memories. Here two PIs (Drs. Josselyn and Frankland), both New Investigators, will combine their expertise to address these important questions. Because all techniques are associated with caveats and limitations, we will use a variety of techniques including optogenetic manipulation, brain-wide neuronal activity mapping and the use of graph-theory to produce “engram maps” and real time in vivo calcium imaging combined with behavior. Together, the ability to manipulate and observe an engram as it forms, changes over time and with behavioral extinction is innovative and may lead to a shift in the very definition of an engram, as well as increase our understanding for developing treatments aimed at resolving inappropriate fear memories.

项目总结/文摘