Anterior Cingulate Cortex preferentially drives dorsal CA1 deep neuronal activity during sharp-wave ripples for memory consolidation

前扣带皮层在锐波波动期间优先驱动背侧 CA1 深层神经元活动以巩固记忆

• 批准号: 10751694
• 负责人: Arron Franklin Hall
• 金额: $ 4.77万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751694
• 关键词: Alzheimer' s Disease; Anatomy; Anterior; Automobile Driving; Behavior; Brain; Cells; Characteristics; Communication; Data; Dementia; Development; Dimensions; Dorsal; Electrophysiology (science); Event; Exhibits; Freezing; Functional disorder; Future; Hippocampus; Hour; Impairment; Intervention; Learning; Linear Models; Mediator; Medical; Memory; Memory Disorders; Nature; Neurons; Pathologic; Pathway interactions; Performance; Phase; Play; Population; Post-Traumatic Stress Disorders; Process; Property; Research Personnel; Role; Shock; Site; Sleep; Slow-Wave Sleep; System; Techniques; Testing; Therapeutic; Therapeutic Intervention; Time; Training; Wakefulness; cingulate cortex; conditioned fear; excitatory neuron; experience; extracellular; fear memory; hippocampal pyramidal neuron; in vivo; independent component analysis; long term memory; memory acquisition; memory consolidation; memory encoding; memory process; neural; neural network; novel; optogenetics; recruit; response; success; therapeutic development

Project Summary: Memory consolidation is an indispensable function for everyday experiences that becomes compromised in many prevalent memory disorders such as post-traumatic stress disorder and dementia. Understanding the underlying process of memory consolidation is essential for the development of therapeutics and treatment interventions for pervasive memory disorders. Systems consolidation, memory consolidation across neural networks, involves the transformation of impermanent, hippocampus-dependent memories, into permanent long-term memories stored throughout cortical regions. During this consolidation process, sharp-wave ripples (SPWs), neural oscillations originating from the dorsal CA1 of the hippocampus during slow wave sleep (SWS), have emerged as a key mediator. These oscillations facilitate systems consolidation through the reactivation of hippocampal and cortical neurons previously active during wakefulness. Recently, researcher have identified two anatomically distinct CA1 pyramidal sublayers that differ in function during SPWs: superficial and deep. Superficial neurons (CA1sup) display more stable firings rates exhibiting little change in response to learning, whereas deep neurons (CA1deep) are less stable exhibiting dynamic changes to learning. While these differences have been uncovered, much remains unknown on how sublayers are selectively recruited during SPWs. The anterior cingulate cortex (ACC), a cortical region involved long-term memory, emerges as a possible candidate in driving CA1 activity. The ACC exhibits increased activity immediately preceding SPWs and dCA1 neuronal firings, suggesting a potential ACC → dCA1 influence. Our results revealed that ACC neural activity immediately preceding SPWs (~200ms prior) preferentially predicts CA1deep neuron activity during SPWs. Prediction success increases following learning, suggesting a role of ACC → CA1deep communication in learning. Additionally, we show that stimulation of ACC excitatory neurons specifically increases the activity of CA1deep, but not CA1sup, during SWS. Given these findings, I hypothesize that ACC neurons selectively communicate with CA1deep activity during SPWs post-learning, and this communication is necessary for consolidation of newly-acquired memories. I will test this hypothesis through the following two aims. Aim 1 will utilize dual-site extracellular in vivo electrophysiology to determine how the ACC and dCA1 neurons communicate during SPW events for memory consolidation. Aim 2 will implement closed-loop optogenetics to investigate the causal role ACC → CA1deep communication during SPWs in memory consolidation. Findings from this proposal will advance our understanding of systems consolidation and how the brain stores long-term memories. Results from this study would lay the framework for the development of future therapeutic interventions targeted towards memory disorders.

项目概要： 记忆巩固是一个不可或缺的功能，为日常经验，成为妥协， 许多流行的记忆障碍，如创伤后应激障碍和痴呆症。了解 记忆巩固的基本过程对于治疗和治疗的发展至关重要 广泛性记忆障碍的干预措施。系统整合，跨神经系统的记忆整合 网络，涉及到将非永久性的，依赖于校园的记忆转化为永久性的记忆。 长期记忆储存在整个皮层区域。在这个巩固过程中， （SPWs），在慢波睡眠期间起源于海马背侧CA1的神经振荡 (SWS)，已经成为一个关键的调解人。这些振荡促进了系统的整合， 海马和皮层神经元在清醒时重新激活。最近，研究人员 已经确定了两个解剖学上不同的CA1锥体亚层，它们在SPW期间的功能不同： 肤浅和深刻。浅表神经元（CA1sup）显示出更稳定的放电率，表现出几乎没有变化， 对学习的反应，而深层神经元（CA 1 deep）不太稳定，表现出动态变化， 学习虽然这些差异已经被发现，但关于子层是如何形成的， 在SPW期间有选择地招募。前扣带皮层（ACC）是一个长期受累的皮层区域， 记忆，作为一个可能的候选人出现在驱动CA1活动。ACC的活性增加 紧接着SPW和dCA 1神经元放电，表明潜在的ACC → dCA 1影响。我们 结果显示，ACC神经活动紧接在SPW之前（约200 ms之前）优先预测 SPW期间CA1深层神经元活动。预测成功率随着学习而增加，这表明 ACC → CA1学习中的深度交流。此外，我们发现，刺激ACC兴奋性神经元， 在SWS期间，特异性地增加CA1deep的活性，而不是CA1sup。鉴于这些发现，我 假设ACC神经元在学习后SPW期间选择性地与CA1深层活动进行通信， 这种通信对于巩固新获得的记忆是必要的。我将检验这个假设 通过以下两个目标。目的1将利用双位点细胞外在体电生理学来确定 ACC和dCA1神经元如何在SPW事件期间进行通信以巩固记忆。目标2将 实施闭环光遗传学来研究ACC → CA1深度通信在 内存整合中的SPW。这项提案的发现将促进我们对系统的理解 以及大脑如何储存长期记忆。这项研究的结果将奠定框架 用于开发针对记忆障碍的未来治疗干预。