Circuit mechanisms of retrospective memory-linking

回顾性记忆链接的电路机制

• 批准号: 10192979
• 负责人: Denise Jade Cai
• 金额: $ 1.16万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192979
• 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.

项目摘要/摘要 创伤后应激障碍(PTSD)症状通常是由以下环境刺激引发的 在创伤过程中不直接出现，但仍会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 通过共享重叠的神经来链接在时间上接近(即，5小时)编码的不同上下文记忆 集合，使得对一个记忆的回忆更有可能触发对另一个在时间上编码的记忆的回忆。 我的实验室有初步证据表明，增加记忆的负效价会延长时间 追溯链接的窗口，使对厌恶环境的恐惧与中性刺激联系在一起 经历过的几天前。将令人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联系起来可能是 适应不良，并可能促进创伤后应激障碍症状。长期观察动态合奏活动 ，我与人共同开发了一种无线迷你镜，它允许在体内自由、自由地进行钙成像 行为不端的老鼠。使用迷你镜，我们发现中性记忆和厌恶记忆通过增加 他们的海马神经系中存在重叠，这种重叠是在学习后的某个时候出现的。我们会 因此，验证这样一种假设，即厌恶体验增强记忆联系是通过 在离线整合期间存储器表示的共同重新激活。我们将测试充分性和 厌恶记忆与SAFE联系中整体激活的必要性以及突触的可塑性 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可能是如何 临床上有针对性的。