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.

项目摘要： 记忆整合是每天经历的必不可少的功能，该功能被妥协 许多流行的记忆障碍，例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发展和治疗的发展至关重要 普遍存在记忆障碍的干预措施。系统合并，中性跨内存的内存合并 网络涉及无常的海马依赖性记忆的转化， 长期存储在整个皮质区域。在此整合过程中，锋利的波浪 （SPW），慢波睡眠期间来自海马的背侧CA1的神经振荡 （SWS）已成为关键调解人。这些振荡通过 先前在清醒期间活跃的海马和皮质神经元的重生。最近，研究员 已经确定了两个在SPWS期间功能不同的解剖学上不同的CA1锥体子层： 肤浅而深层。表面神经元（CA1SUP）显示出更稳定的射击率，几乎没有变化 对学习的反应，而深神经元（Ca1deep）较不稳定，表现出动态变化 学习。尽管这些差异已经被发现，但对于子层的方式仍然未知 在SPWS期间有选择地招募。前扣带回皮质（ACC），一个皮质区域涉及长期 记忆是驱动CA1活动的可能候选者。 ACC表现出增加的活动 紧接在SPW和DCA1神经元发射之前，表明潜在的ACC→DCA1影响。我们的 结果表明，在SPW之前紧接的ACC神经活动（先前约200ms）优先预测 SPWS期间的Ca1Deep神经元活性。学习后的预测成功增加了，这表明 ACC→学习中的Ca1Deep沟通。此外，我们表明刺激ACC兴奋性神经元 在SWS期间，特别增加了Ca1deep（而不是Ca1sup）的活性。有了这些发现，我 假设ACC神经元在学习后SPW中选择性地与CA1DEEP活动进行交流，并且 这种通信对于合并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。 AIM 1将利用双位点细胞外体内电生理学来确定 ACC和DCA1神经元在SPW事件中如何进行记忆巩固。 AIM 2意志 实施了闭环光遗传学，以研究因果关系→Ca1deep通信 记忆合并中的SPW。该提案的发现将提高我们对系统的理解 整合以及大脑如何存储长期记忆。这项研究的结果将构成框架 为了开发针对记忆障碍的未来治疗干预措施。