Probing of cortical-hippocampal dialogue using light-mediated circuit monitoring in vivo

我们一生中大约有三分之一的时间在睡觉。也许令人惊讶的是，我们的大脑从不休息，神经元在睡眠中保持持续活跃。人们可以推断，负责自主神经功能（如呼吸）的神经元在睡眠和清醒时都应该是活跃的，然而，为什么大脑其他部分的神经元在睡眠期间经常以高度同步和有节奏的方式保持活跃？一种被提出的观点是，睡眠期间的神经活动可能允许神经连接的重新布线，而这种突触的重新布线与存储记忆有关。我的重点是理解需要海马等内侧颞叶结构的记忆。情景记忆)以及睡眠中出现在新皮质（NC）和海马体（HPC）的特定自发活动模式对记忆的增强作用。我研究的中心目标是提供关于睡眠期间HPC和NC相互作用的新信息。尽管有证据表明这些记忆是通过海马体锐波振荡（SPW）和皮质慢波振荡（SO）之间的功能耦合形成的，但它们如何相互作用以支持信息传递仍不清楚。为了提供关于睡眠中HPC和NC相互作用的新见解，我们将把新的成像技术与最先进的遗传、分子和电生理技术相结合。这将使我们能够在单个突触的水平上询问皮层回路，并利用来自海马体的信息以毫秒级的时间分辨率在整个皮层上运行。我研究的主要目的是研究SO和SPW-以及其他事件（如纺锤波、伽马振荡）是如何嵌入到更大的皮层网络中的。通过选择性地暂时停用SPW，我将测试HPC活动和NC不同网络活动模式之间的因果关系。此外，我将剖析如何HPC输出到NC显著贡献经验依赖的树突脊柱的转换和可塑性。这些实验的开展将有助于我们更深入地了解海马和新皮层与信息加工和长期记忆储存之间的功能关系。

We spend about one third of our lives sleeping. Perhaps surprisingly, our brain never rests and neurons remain continually active during sleep. One can reason that neurons responsible for autonomic functions such as respiration should be active in both sleep and wakefulness, however, why would neurons in other parts of the brain remain active, often in a highly synchronous and rhythmic fashion during sleep? One proposed idea is that neural activity during sleep may allow for the rewiring of neural connections and that this synaptic rewiring is relevant for storing memories. My focus is on understanding memories that require medial temporal lobe structures like the hippocampus (eg. episodic memory) and the memory-enhancing role of particular patterns of spontaneous activity that appear during sleep in neocortex (NC) and hippocampus (HPC). The central goal of my research is to provide new information regarding the interaction of HPC and NC during sleep. Although evidence indicates that these memories are formed through a functional coupling between hippocampal sharp-wave (SPW) and cortical slow-wave oscillations (SO), how they interact to subserve a transfer of information is still unclear. To provide new insight regarding the interaction of HPC and NC during sleep, we will combine novel imaging technologies with the most advanced genetic, molecular and electrophysiological technologies. This will allow us to interrogate the cortical circuits at the level of individual synapses and function with millisecond temporal resolution across the entire cortex with information from the hippocampus. The primary aim of my research will be to examine how SO and SPW-, and other events (i.e. spindles, gamma oscillations) are embedded in larger cortical networks. By selectively and temporarily inactivating SPW, I will test a causal link between HPC activity and NC distinct network activity patterns. Further, I will dissect how HPC output to NC contributes significantly to experience-dependent dendritic spine turnover and plasticity. Performing these experiments will provide a deeper understanding of the functional relationship between hippocampus and neocortex and information processing and long-term memory storage.