Thalamic gating during sleep oscillations

睡眠振荡期间的丘脑门控

• 批准号: RGPIN-2018-06291
• 负责人: Timofeev, Igor
• 金额: $ 4.23万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714200
• 关键词: Thalamic; gating; during; sleep; oscillations

Background: I am interested in the understanding of physiological basis of conscious states, which are essentially cortical phenomena. Almost all information reaching cerebral cortex passes through the thalamus that is a key element in the understanding of cortical function. Morphology and physiology of sensory thalamus and thalamocortical system (somatosensory, visual etc) is known. However, the role of midline thalamic nuclei (MTN) remains largely obscure. Neurons from these nuclei are likely responsible for the generation of conscious vs. unconscious states and different levels of alertness. I propose to investigate not only how these neurons are implicated in the generation of brain states, but also how a modification of their excitability could affect behavioral performance. Objectives: (1) To evaluate the main sources of inhibition in MTN, (2) to evaluate patterns of activity of MTN during brain activated states (wake, REM sleep) vs. slow-wave sleep, (3) to manipulate MTN excitability and to affect the expression of sleep-wake states and behavioral performance. Hypothesis: Thalamocortical neurons from MTN provide control of cortical excitability and mediate generation of states, like sleep and wake. They control levels of alertness. Methods: (1) Retrograde labeling to determine the main inputs to MTN, combined with optogenetic stimulation and electrophysiological recordings. (2) Intracellular recordings in vivo from MTN neurons during brain oscillatory states (mainly anesthesia). (3) Neuronal firing recording from MTN neurons during different states of vigilance. (4) Pharmacogenetic modulation of MTN excitability and its effects on sleep-wake cycle as well as behavioral performance. Originality and feasibility: Very few studies investigated MTN; no intracellular recordings from these cells are available in the literature. Therefore, everything proposed above will be new. Intracellular recording technique is very complex and difficult to do on mice. My laboratory pioneered intracellular recordings in non-anesthetized animals; it also recently published a number of papers where intracellular recordings were done on mice, therefore the technically complex experiments appear feasible. Contribution to the advancement of knowledge: Systematic knowledge on the role of MTN neurons in brain functions does not exist. We propose series of experiments to investigate what role these nuclei play in the generation of states of vigilance and overall alertness.

背景：我对意识状态的生理基础的理解感兴趣，意识状态本质上是皮层现象。几乎所有到达大脑皮层的信息都要经过丘脑，丘脑是理解皮层功能的关键因素。感觉丘脑和丘脑皮质系统（躯体感觉、视觉等）的形态学和生理学是已知的。然而，中线丘脑核（MTN）的作用在很大程度上仍然是模糊的。来自这些核团的神经元可能负责产生有意识和无意识状态以及不同水平的警觉性。我建议不仅要研究这些神经元如何参与大脑状态的产生，而且还要研究它们的兴奋性的改变如何影响行为表现。 目的：（1）评估MTN中抑制的主要来源，（2）评估脑激活状态（觉醒、REM睡眠）与慢波睡眠期间MTN的活动模式，（3）操纵MTN兴奋性并影响睡眠-觉醒状态和行为表现的表达。 假设：来自MTN的丘脑皮质神经元提供皮质兴奋性的控制，并介导状态的产生，如睡眠和觉醒。它们控制着警觉的程度。 方法：（1）采用逆行标记技术，结合光遗传学刺激和电生理记录，确定MTN的主要输入。(2)脑振荡状态（主要是麻醉）期间MTN神经元的体内细胞内记录。(3)不同警觉状态下MTN神经元的放电记录。(4)MTN兴奋性的药物遗传学调节及其对睡眠-觉醒周期和行为表现的影响。 独创性和可行性：很少有研究调查MTN，没有细胞内记录这些细胞在文献中。因此，上面提出的一切都将是新的。细胞内记录技术非常复杂，在小鼠身上很难做到。我的实验室率先在非麻醉动物中进行细胞内记录;它最近也发表了一些论文，其中细胞内记录是在小鼠身上完成的，因此技术复杂的实验似乎是可行的。 对知识进步的贡献：关于MTN神经元在脑功能中的作用的系统知识并不存在。我们提出了一系列的实验，以调查这些核在警觉和整体警觉状态的产生中起着什么样的作用。