Weak electric current stimulation and optogenetics to investigate sleep-dependent memory consolidation and ensemble reactivation

关于睡眠相关海马依赖性记忆巩固的研究主要集中在非快速眼动睡眠期间海马的再激活和海马-前额叶的相互作用。最近，丘脑基质核作为海马体-前额叶双向相互作用的枢纽的作用引起了人们的兴趣。在之前的资助期间，我们开发了使用光遗传和闭环弱电刺激来询问前额叶和海马网络振荡的工具。我们的研究结果表明，内源性振荡可以由光遗传刺激引起。此外，节律动力学的诱导变化影响了探索行为，并再现了自发同步和行为之间的相关性，表明了因果功能联系。其他人的研究和我们的初步发现表明，模拟阈下活动的弱电刺激对反映行为和警惕性状态依赖性的持续网络振荡最为敏感。睡眠期间的记忆巩固与跨区域网络振荡的协调有关，如睡眠缓慢振荡。在这里，使用实验和分析工具，我们将在项目中开发，我们的目标首先是定义一个跨区域的活动模式，预测记忆的获取和巩固。其次，采用多区域闭环弱电和光遗传刺激方案，我们旨在通过操纵其内源性电生理特征来改善睡眠相关记忆巩固。第三，在此过程中，我们将开发新的光遗传和弱电网络检测工具。

Investigations on the consolidation of sleep-associated hippocampus dependent memories have focussed on hippocampal reactivation and hippocampo-prefrontal interactions during non-rapid eye movement sleep. Recently, the role of thalamic matrix nuclei as a hub for bidirectional hippocampal-prefrontal interactions has become of interest. In the previous funding period we developed tools to interrogate prefrontal and hippocampal network oscillations using optogenetic and closed-loop weak electric current stimulation. Our results revealed that endogenous oscillations can be entrained by optogenetic stimulation. Moreover, induced changes in the rhythm dynamics affected exploratory behaviour and recapitulated correlations between spontaneous synchronization and behaviour indicating a causal functional connection. Studies of others and our preliminary findings suggest that the effects of weak electric current stimulation, which simulates subthreshold activity, are most sensitive to ongoing network oscillations reflecting behavioural and vigilance state-dependence. Memory consolidation during sleep is linked to the orchestration of cross-regional network oscillations, as the sleep slow oscillation. Here, using experimental and analytical tools to-be developed in the project we aim firstly to define a cross-regional pattern of activity predictive of memory acquisition and consolidation. Secondly, employing multi-regional closed-loop weak electrical and optogenetic stimulation protocols we aim to improve sleep-associated memory consolidation by manipulating its endogenous electrophysiological signatures. Thirdly, in this process we will develop novel tools for optogenetic and weak electric network interrogation.