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

基本信息

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
项目类别：
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&apos 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

项目摘要

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：记忆巩固是日常体验中不可或缺的功能，但在日常体验中，记忆巩固会受到影响。许多流行的记忆障碍，例如创伤后应激障碍和痴呆症。记忆巩固的基本过程对于治疗方法的发展至关重要普遍性记忆障碍的干预措施，跨神经的记忆巩固。网络，涉及将永久的、依赖海马体的记忆转变为永久的在这个巩固过程中，长期记忆储存在整个皮质区域。 (SPWs)，慢波睡眠期间源自海马背侧 CA1 的神经振荡（SWS）已成为关键的调解者，这些振荡通过以下方式促进了系统整合。最近，研究人员发现，先前在清醒状态下活跃的海马和皮质神经元被重新激活。已经确定了两个解剖学上不同的 CA1 锥体亚层，它们在 SPW 期间功能不同：浅层和深层神经元（CA1sup）表现出更稳定的放电率，几乎没有变化。对学习的反应，而深层神经元 (CA1deep) 则不太稳定，表现出动态变化虽然这些差异已经被发现，但关于子层是如何进行的仍有很多未知之处。在 SPW 期间选择性地招募前扣带皮层 (ACC)，这是一个涉及长期的皮质区域。记忆，可能是驱动 CA1 活动的候选者，ACC 表现出活动增加。紧接在 SPW 和 dCA1 神经元放电之前，表明 ACC → dCA1 存在潜在影响。结果显示，紧接在 SPW 之前（约 200 毫秒）的 ACC 神经活动优先预测 SPW 期间的 CA1 深层神经元活动在学习后会增加，这表明 ACC → CA1 学习中的深层沟通此外，我们还发现 ACC 兴奋性神经元的刺激。鉴于这些发现，我在 SWS 期间特别增加了 CA1deep 的活性，但不增加 CA1sup 的活性。确保 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，以及这种交流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，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 事件期间如何进行通信以巩固记忆。实施闭环光遗传学来研究 ACC → CA1 深层通讯的因果作用该提案中的 SPW 的发现将增进我们对系统的理解。这项研究的结果将奠定框架。开发针对记忆障碍的未来治疗干预措施。