CRNS: An Integrative Study of Hippocampal-Neocortical Memory Coding during Sleep

睡眠对记忆和学习至关重要。在快速眼动（REM）或非快速眼动（NREM）睡眠期间，海马和感觉皮层回路中的细胞亚群以一种时间协调的方式重新激活，形成了记忆巩固过程中皮层-海马-皮层信息处理回路。破译睡眠时海马体-新皮层记忆的神经密码将揭示记忆巩固的重要回路机制。迄今为止，对睡眠中海马-新皮层记忆加工及其特定空间/非空间记忆表征的相互作用机制缺乏完整的理解。此外，海马体-新皮层相互作用对随后的记忆再激活或睡眠后学习的因果影响知之甚少。在这个提议中，我们将剖析啮齿动物海马CA1和初级视觉皮层（V1）在睡眠期间的空间（“在哪里”）和视觉（“什么”）记忆表征。我们将结合电生理学、群体解码方法、光遗传学和闭环神经接口来解码记忆编码中与睡眠相关的CA1-V1群体编码。在目标1中，我们将识别空间导航任务中的视觉皮层表征，并确定视觉皮层神经元对空间、经验和视觉线索的依赖。在目标2中，我们将揭示睡眠期间CA1-V1记忆再激活的“在哪里”（空间）和“什么”（视觉）表征。在Aim 3中，我们将确定海马体在睡眠期间记忆巩固的V1-CA1-V1回路中的因果作用。总之，这些结果将使我们能够随意剖析睡眠期间海马-新皮层记忆编码的回路机制，并建立一种新的分析范式来识别睡眠期间海马-记忆再激活的内容。我们的项目将进一步深入了解与记忆相关的神经和精神疾病，以及靶向记忆再激活或增强的潜在治疗方法。

Sleep is critical to memory and learning. During rapid eye movement (REM) or non-REM (NREM) sleep, subgroups of cell assemblies in hippocampal and sensory cortical circuits are reactivated in a temporally coordinated manner, forming a cortical-hippocampal-cortical loop of information processing during memory consolidation. Deciphering neural codes of hippocampal-neocortical memories during sleep would reveal important circuit mechanisms of memory consolidation. To date, a complete understanding of the mechanisms of hippocampal-neocortical memory processing and the interaction of their specific spatial/non­ spatial memory representations during sleep is lacking. Furthermore, little is known about the causal impact of the hippocampal-neocortical interactions on subsequent memory reactivation or post-sleep learning. In this proposal, we will dissect representations of spatial ("where") and visual ("what") memory in the rodent hippocampal CA1 and primary visual cortex (V1) during sleep. We will combine electrophysiology, population-decoding methods, optogenetics and closed-loop neural interface to decipher sleep-associated CA1-V1 population codes in memory coding. In Aim 1, we will identify visual cortical representations in a spatial navigation task and determine visual cortical neuronal firing dependency on space, experiences and visual cues. In Aim 2, we will uncover "where" (spatial) and "what" (visual) representations of CA1-V1 memory reactivations during sleep. In Aim 3, we will determine the causal role of the hippocampus in the V1-CA1-V1 loop of memory consolidation during sleep. Together, these results will enable us to casually dissect circuit mechanisms of hippocampal-neocortical memory coding during sleep, and to establish a new analysis paradigm to identify the contents of hippocampal-memory reactivations during sleep. Our project will provide further insight into memory-related neurological and psychiatric disorders and potential therapeutic treatment for targeted memory reactivation or enhancement.