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)睡眠中，海马区和感觉皮层回路中的细胞组合亚群以时间协调的方式重新激活，在记忆巩固过程中形成皮层-海马区-皮质信息处理循环。破译睡眠期间海马区-新皮质记忆的神经编码将揭示记忆巩固的重要电路机制。到目前为止，对海马区-新皮质记忆加工的机制以及它们在睡眠中特定的空间/非空间记忆表征的相互作用还缺乏完整的了解。此外，关于海马体-新皮质相互作用对随后的记忆重新激活或睡眠后学习的因果影响还知之甚少。在这项研究中，我们将剖析啮齿动物海马区CA1和初级视皮层(V1)在睡眠过程中空间记忆(“Where”)和视觉记忆(“What”)的表征。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破译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记忆重新激活的“位置”(空间)和“什么”(视觉)表示。在目标3中，我们将确定海马体在睡眠期间记忆巩固的V1-CA1-V1环路中的因果作用。综上所述，这些结果将使我们能够随意地剖析睡眠中海马-新皮质记忆编码的电路机制，并建立一种新的分析范式来识别睡眠中海马-记忆重新激活的内容。我们的项目将为记忆相关的神经和精神障碍提供进一步的洞察，并提供靶向记忆重新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.