Circuit mechanisms of retrospective memory-linking

回顾性记忆链接的电路机制

• 批准号: 9912892
• 负责人: Denise Jade Cai
• 金额: $ 53.02万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-03 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912892
• 关键词: Affect; Amygdaloid structure; Animals; Behavior; Cells; Clinical; Cues; Data; Development; Emotional; Environment; Event; Fright; Future; Goals; Hippocampus (Brain); Hour; Image; Immediate-Early Genes; Knowledge; Learning; Light; Link; Mediating; Memory; Microscope; Modeling; Mus; Negative Valence; Pathologic; Phase; Post-Traumatic Stress Disorders; Predictive Value; Process; Retrieval; Shock; Stimulus; Symptoms; Synaptic plasticity; System; Techniques; Testing; Time; Trauma; Work; conditioned fear; experience; experimental study; foot; in vivo; in vivo calcium imaging; in vivo imaging; insight; interdisciplinary approach; memory encoding; memory retrieval; novel; prevent; prospective; relating to nervous system; response; sensory stimulus; symptomatology; traumatic event

PROJECT SUMMARY/ABSTRACT Post-traumatic stress disorder (PTSD) symptoms are often triggered by environmental stimuli that were not directly present during trauma, but which nevertheless elicit strong fear responses. Thus, understanding how fear spreads to non-trauma associated stimuli is paramount to PTSD treatment. Recently, I found that different contextual memories encoded close in time (i.e., 5 hours) are linked by sharing an overlapping neural ensemble, making recall of one memory more likely to trigger recall of another memory encoded close in time. My lab has preliminary evidence that increasing the negative valence of a memory extends the temporal window of retrospective linking, such that the fear of an aversive context is linked with neutral stimuli experienced days prior. Linking aversive experiences to past events is ecologically valuable, as the past has predictive value for the future. However, overlinking traumatic experiences to everyday memories could be maladaptive and may promote PTSD symptoms. To observe dynamic ensemble activity across long time scales, I have co-developed a wire-free Miniscope which allows in vivo calcium imaging in untethered, freely behaving mice. Using the Miniscope, we found that neutral and aversive memories are linked by an increased overlap in their hippocampal neural ensembles, and that this overlap emerges sometime after learning. We will therefore test the hypothesis that the enhancement of memory-linking by aversive experience emerges through co-reactivation of memory representations during an offline consolidation period. We will test the sufficiency and necessity of ensemble reactivation, as well as synaptic plasticity, in the linking of aversive memories and safe memories. This work could therefore shed fundamental light on the spread of fear in PTSD and how it might be clinically targeted.

项目总结/摘要 创伤后应激障碍（PTSD）症状通常由环境刺激引发， 在创伤期间不直接出现，但仍然引起强烈的恐惧反应。因此，理解 恐惧如何传播到非创伤相关的刺激对创伤后应激障碍的治疗至关重要。最近我发现 在时间上接近编码的不同上下文记忆（即，5小时）通过共享一个重叠的神经网络 整体，使回忆一个记忆更有可能触发回忆另一个记忆编码接近的时间。 我的实验室有初步证据表明增加记忆的负效价会延长 回顾性链接窗口，使对厌恶性背景的恐惧与中性刺激相关联 前几天经历过。将令人厌恶的经历与过去的事件联系起来，就像过去一样， 对未来的预测价值。然而，将创伤经历与日常记忆联系起来， 适应不良，并可能促进创伤后应激障碍症状。观察长时间的动态集合活动 我与人合作开发了一种无导线的微型显微镜，它可以在体内进行钙成像， 行为老鼠使用迷你镜，我们发现中性和厌恶性记忆是由增加的 在他们的海马神经系统中有重叠，这种重叠在学习后的某个时候出现。我们将 因此，我们要验证这样一个假设，即厌恶性经历对记忆联系的增强是通过以下方式出现的： 在离线巩固期间记忆表征的共同再激活。我们将测试其充分性， 整体再激活的必要性，以及突触可塑性，在连接厌恶性记忆和安全 回忆因此，这项工作可以从根本上阐明创伤后应激障碍中恐惧的传播以及它是如何传播的。 临床针对性