Thalamic control of cortical dynamics during slow wave sleep via GABAergic interneurons

丘脑通过 GABA 能中间神经元控制慢波睡眠期间的皮质动力学

• 批准号: BB/S015922/1
• 负责人: Ole Paulsen
• 金额: $ 60.05万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS015922%2F1
• 关键词: Thalamic; control; cortical; dynamics; during

We sleep almost one third of our life and adequate sleep is necessary for mental health. Indeed, lack of sleep is associated with attention deficit, fatigue, reduced performance and increased risk of obesity and other diseases. Sleep is essential for memory. For the memory of today's events to stick in our brains, a good night's sleep is necessary. More precisely, it is the deep sleep stages that are crucial for memory. These stages occur primarily during the first sleep cycles early during the night. They are characterised by synchronous activity throughout the brain. The synchronisation of neuronal activity is necessary for memory bits to be transferred from one brain area to another and for them to be consolidated or eliminated. A brain that lacks this synchronisation property would lose its ability to organise and retain information. We want to understand where this synchronisation comes from and what mechanisms are responsible. We have identified a site in the brain known as higher-order thalamic nuclei that could act as a conductor of brain synchronisation of neuronal activity.We will investigate this in mice by studying how disrupting the thalamic activity affects the synchronicity of neuronal activity. To control the thalamic activity we will use a new technique known as optogenetics, which permits us to activate or silence part of the mouse brain using a laser. Simultaneously we will use electrical recording of brain activity to evaluate the degree of synchronisation. We will test whether activating the thalamus with precise timing would enhance synchronisation of brain areas and whether silencing the thalamus would disorganise the brain synchronicity. The results of this study would identify a conductor for neuronal synchronisation and give insight into how to improve sleep quality.

我们几乎有三分之一的时间在睡觉，充足的睡眠对心理健康是必要的。事实上，睡眠不足与注意力缺陷、疲劳、表现下降以及肥胖和其他疾病的风险增加有关。睡眠对记忆至关重要。为了让今天发生的事情牢牢地留在我们的脑海里，一夜好觉是必要的。更确切地说，深度睡眠阶段对记忆至关重要。这些阶段主要发生在夜间早些时候的第一个睡眠周期期间。它们的特点是整个大脑的同步活动。神经元活动的同步对于记忆比特从一个大脑区域转移到另一个大脑区域以及巩固或消除它们是必要的。缺乏这种同步特性的大脑将失去组织和保留信息的能力。我们想了解这种同步来自哪里，以及是什么机制负责。我们已经在大脑中发现了一个被称为高级丘脑核的部位，它可以作为大脑神经元活动同步的导体。我们将通过研究丘脑活动的破坏如何影响神经元活动的同步性来研究小鼠。为了控制丘脑活动，我们将使用一种称为光遗传学的新技术，它允许我们使用激光激活或沉默小鼠大脑的一部分。同时，我们将使用大脑活动的电子记录来评估同步程度。我们将测试在精确的时间激活丘脑是否会增强大脑区域的同步性，以及沉默丘脑是否会扰乱大脑的同步性。这项研究的结果将确定神经元同步的导体，并深入了解如何提高睡眠质量。

项目成果

Brainstem cholinergic modulation of the thalamocortical activity in urethane anesthetized mice

乌拉坦麻醉小鼠丘脑皮质活动的脑干胆碱能调节

• DOI: 10.1101/2021.05.12.443746
• 发表时间: 2021
• 作者: Hay Y

Partial restoration of physiological UP-state activity by GABA pathway modulation in an acute brain slice model of epilepsy

在癫痫急性脑切片模型中通过 GABA 通路调节部分恢复生理 UP 状态活动

• DOI: 10.1016/j.neuropharm.2018.11.032
• 发表时间: 2019
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Koerling A