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

弱电流刺激和光遗传学研究睡眠依赖性记忆巩固和整体重新激活

• 批准号: 238646609
• 负责人: Professorin Dr. Lisa Marshall
• 金额: --
• 依托单位: Institut für Physiologie und Pathophysiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/238646609?language=en
• 关键词: Weak; electric; current; stimulation; optogenetics

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.

对睡眠相关海马依赖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，丘脑基质核团作为双向前额叶-海马相互作用的枢纽的作用已成为兴趣。在上一个资助期，我们开发了使用光遗传学和闭环弱电流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，内源性振荡可以夹带由光遗传学刺激。此外，诱导的变化的节奏动力学影响探索的行为和概括的自发同步和行为之间的相关性，表明因果功能连接。其他人的研究和我们的初步研究结果表明，弱电流刺激，模拟阈下活动的影响，是最敏感的正在进行的网络振荡，反映行为和警惕状态依赖。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，将在该项目中开发，我们的目标是首先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学刺激方案，我们的目标是通过操纵其内源性电生理特征来改善睡眠相关的记忆巩固。第三，在这个过程中，我们将开发用于光遗传学和弱电网络询问的新工具。