Circuit mechanisms of retrospective memory-linking

回顾性记忆链接的电路机制

• 批准号: 10064148
• 负责人: Denise Jade Cai
• 金额: $ 53.08万
• 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/10064148
• 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.

项目概要/摘要 创伤后应激障碍 (PTSD) 症状通常是由环境刺激引发的 在创伤期间不直接出现，但仍然引起强烈的恐惧反应。因此，了解 恐惧如何传播到非创伤相关的刺激对于 PTSD 治疗至关重要。最近，我发现 时间相近（即 5 小时）编码的不同上下文记忆通过共享重叠的神经网络连接起来 整体，使得对一个记忆的回忆更有可能触发对时间相近编码的另一记忆的回忆。 我的实验室有初步证据表明，增加记忆的负价可以延长时间 回顾性联系的窗口，使得对厌恶环境的恐惧与中性刺激联系起来 前几天经历过。将厌恶的经历与过去的事件联系起来具有生态价值，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过度联系可能会 适应不良并可能促进 PTSD 症状。观察长时间内的动态系综活动 我与他人共同开发了一种无线微型显微镜，可以不受束缚、自由地进行体内钙成像 行为老鼠。使用迷你显微镜，我们发现中性记忆和厌恶记忆通过增加的 他们的海马神经元存在重叠，并且这种重叠在学习后的某个时候就会出现。我们将 因此，检验以下假设：厌恶经历对记忆联结的增强是通过以下方式出现的： 在离线巩固期间共同重新激活记忆表征。我们将测试充分性和 在厌恶记忆和安全记忆的联系中，整体重新激活以及突触可塑性的必要性 回忆。因此，这项工作可以从根本上揭示创伤后应激障碍中恐惧的传播以及它可能如何传播。 临床针对性。