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

项目总结： 记忆巩固是日常体验不可或缺的功能，而日常体验在 许多普遍的记忆障碍，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是必不可少的 对广泛性记忆障碍的干预。系统整合，跨神经的记忆整合 网络，包括将非永久性的、依赖于海马体的记忆转变为永久性的 存储在大脑皮层区域的长期记忆。在这一巩固过程中，尖锐的波纹 (SPW)，慢波睡眠时源自海马区背侧CA1的神经振荡 (SWS)，已经成为关键的调解人。这些振荡通过以下方式促进系统整合 重新激活以前在清醒状态下活跃的海马神经元和皮质神经元。最近，研究人员 已经确定了在SPW期间功能不同的两个解剖上不同的CA1锥体亚层： 肤浅而深刻。浅层神经元(CA1sup)表现出更稳定的放电率，几乎没有变化 对学习的反应，而深部神经元(CA1深)不太稳定，表现出动态变化 学习。虽然这些差异已经被发现，但关于子层的情况仍有许多未知之处 在特殊目的战争期间被选择性地招募。前扣带回(ACC)是一个长期受累的皮质区域 记忆，是驱动CA1活动的一个可能的候选者。ACC表现出更多的活动 紧接在SPW和DCA1神经元放电之前，暗示了潜在的Acc→DCA1影响。我们的 结果显示，紧靠在SPW之前的ACC神经活动(大约200ms之前)优先预测 SPW时CA1深层神经元的活动。预测的成功率随着学习而增加，这表明 Acc→CA1在学习中进行深度交流。此外，我们还发现，刺激ACC兴奋性神经元 特别是在SWS期间增加CA1Deep的活性，但不增加CA1sup的活性。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，以及 这种交流对于巩固新获得的记忆是必要的。我将检验这一假设 通过以下两个目标。AIM 1将利用体内细胞外双部位电生理学来确定 在SPW事件中，ACC和dCA1神经元如何进行通讯以巩固记忆。目标2将 应用闭环光遗传学研究→CA1深层通讯在脑内的因果作用 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 巩固和大脑如何存储长期记忆。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措施。

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.