Circuit mechanisms of retrospective memory-linking

回顾性记忆链接的电路机制

• 批准号: 10517282
• 负责人: Denise Jade Cai
• 金额: $ 49.08万
• 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/10517282
• 关键词: Affect; Amygdaloid structure; Animals; Behavior; Cells; Clinical; Cues; Data; Development; Emotional; Environment; Event; Fright; Future; Genetic; Genetic Techniques; Goals; Hippocampus; Hour; Image; Immediate-Early Genes; Knowledge; Learning; Link; Mediating; Memory; Microscope; Modeling; Mus; Negative Valence; Pathologic; Phase; Post-Traumatic Stress Disorders; Predictive Value; Process; Retrieval; Shock; Stimulus; Symptoms; Synaptic plasticity; System; Testing; Time; Trauma; Work; conditioned fear; experience; experimental study; foot; genetic manipulation; in vivo; in vivo calcium imaging; in vivo imaging; insight; interdisciplinary approach; memory acquisition; memory encoding; memory retrieval; neural; novel; prevent; prospective; 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）症状通常是由环境刺激引起的 不直接存在创伤期间，而是引起强烈的恐惧反应。因此，理解 恐惧如何扩散到非创伤相关的刺激中对于PTSD治疗至关重要。最近，我发现 通过共享一个重叠的神经来链接到近距离编码的不同上下文记忆（即5小时） 合奏，让回忆一个内存更有可能触发对另一个记忆的回忆，该记忆的时间是及时编码的。 我的实验室有初步证据表明，增加内存的负价扩展了时间。 回顾性链接的窗口，使人们对厌恶背景的恐惧与中性刺激有关 经验前几天。将厌恶经验与过去的事件联系起来是很有价值的，因为过去 未来的预测价值。但是，将创伤性经历与日常记忆的重叠可能是 适应不良，可能促进PTSD症状。长时间观察动态合奏活动 鳞片，我共同开发了一个无线的米斯科托，该丝房允许体内钙成像不受限制，自由地 行为小鼠。使用Miniscope，我们发现中性和厌恶记忆与增加有关 在其海马神经合奏中重叠，并且这种重叠在学习后的某个时候出现。我们将 因此，检验了以下假设，即通过厌恶经验增强记忆链接的增强 在离线合并期间内存表示的共反射。我们将测试充分性和 在厌恶记忆和安全的连接中，需要重新激活以及突触可塑性 回忆。因此，这项工作可能会阐明恐惧在PTSD中的传播及其可能如何 临床针对性。