Thalamic gating during sleep oscillations

背景：我对理解意识状态的生理基础很感兴趣，意识状态本质上是一种皮层现象。几乎所有到达大脑皮层的信息都要经过丘脑，这是理解皮层功能的一个关键因素。感觉丘脑和丘脑皮质系统（体感、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不清楚。来自这些核的神经元可能负责产生有意识和无意识状态以及不同程度的警觉性。我建议不仅要研究这些神经元如何与大脑状态的产生有关，还要研究它们的兴奋性的改变如何影响行为表现。

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.