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

关于睡眠相关的海马区依赖记忆巩固的研究主要集中在非快速眼动睡眠时海马区的重新激活和海马区-前额叶之间的相互作用。最近，丘脑基质核作为双向海马-前额叶相互作用的中枢的作用引起了人们的兴趣。在之前的资助期间，我们开发了使用光发生和闭路弱电流刺激来询问前额叶和海马区网络振荡的工具。我们的结果表明，内源性振荡可以通过光遗传刺激来实现。此外，节律动态的诱发变化影响探索行为，并概括了自发同步和行为之间的相关性，表明存在因果功能联系。其他人的研究和我们的初步发现表明，模拟阈值下活动的弱电流刺激的影响，对反映行为和警觉状态依赖的持续网络振荡最敏感。睡眠期间的记忆巩固与跨区域网络振荡的协调有关，即睡眠缓慢振荡。在这里，利用实验和分析工具，我们的目标是首先定义记忆获得和巩固的跨区域活动预测模式。其次，采用多区域闭环弱电刺激和光遗传刺激方案，旨在通过操纵睡眠相关的内源性电生理信号来改善睡眠相关记忆的巩固。第三，在这一过程中，我们将开发用于光伏发电和弱电网络讯问的新型工具。

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.