Non-Neuronal Sleep/Wake Control in Cortex

皮层的非神经元睡眠/唤醒控制

基本信息

批准号：
10356161
负责人：
GRAEME W DAVIS
金额：
$ 40.63万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-06 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10356161
关键词：
Acetylcholine Address Animal Behavior Animals Area Astrocytes Basic Science Biological Brain Brain Stem Calcium Cells Cerebral cortex Dopamine Electrophysiology (science)Exhibits Fiber Future Glutamates Goals Health Histamine Histamine H1 Receptors Histamine Receptor Human Image Knowledge Maps Measures Mental disorders Metabolic Diseases Modeling Modernization Molecular Neurobiology Neuroglia Neuromodulator Neurons Norepinephrine Optics Outcome Output Physiological Physiology Population Potassium Process Receptor Activation Receptor Signaling Regulation Research Role Signal Transduction Sleep System Techniques Technology Testing Work cell type extracellular in vivo mammilloinfundibular nucleus structure nervous system disorder neural circuit neuronal circuitry neuroregulation neurotransmission receptor expression relating to nervous system response sleep regulation spatiotemporal targeted treatment tool two-photon

Acetylcholine Address Animal Behavior Animals Area Astrocytes Basic Science Biological Brain Brain Stem Calcium Cells Cerebral cortex Dopamine Electrophysiology (science)Exhibits Fiber Future Glutamates Goals Health Histamine Histamine H1 Receptors Histamine Receptor Human Image Knowledge Maps Measures Mental disorders Metabolic Diseases Modeling Modernization Molecular Neurobiology Neuroglia Neuromodulator Neurons Norepinephrine Optics Outcome Output Physiological Physiology Population Potassium Process Receptor Activation Receptor Signaling Regulation Research Role Signal Transduction Sleep System Techniques Technology Testing Work cell type extracellular in vivo mammilloinfundibular nucleus structure nervous system disorder neural circuit neuronal circuitry neuroregulation neurotransmission receptor expression relating to nervous system response sleep regulation spatiotemporal targeted treatment tool two-photon

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项目摘要

Sleep and wake are critical for animal survival, but the mechanisms by which the brain coordinates switching between these brain states, from brainstem to cortex, remains unclear. Neuromodulatory signaling circuits are essential systems for brain state switching, both in sleep/wake and in other contexts. In the current proposal, we explore the role of one of these neuromodulators—histamine—in the regulation of sleep and wake in the cerebral cortex. Although histamine has long been known as a wake-promoting neuromodulator, it is relatively understudied compared to others, so our understanding of its cellular and circuit mechanisms of action is still in the early stages. Here, we take a holistic perspective of the cell types involved in sleep/wake circuits, and ask how the largest class of non-neuronal cells in the brain, astrocytes, are involved in sending and responding to histaminergic signals in the cortex. We aim to address gaps in our knowledge of sleep/wake dynamics, histaminergic signaling, and astrocytic regulation of neural circuits by uncovering critical cell biological signaling systems in astrocytes. We apply advanced optical, electrophysiological, and neural manipulation techniques to reveal how astrocytes may be integrating neuromodulatory signals in cortical circuits and coordinating populations of neurons. Our main goals include: probing the cell biological mechanisms by which histamine activates astrocytes, testing the spatiotemporal dynamics of histamine and astrocytes to determine their causal relationships, and exploring the mechanisms by which astrocytes may synchronize or desynchronize neuronal activity.

睡眠和唤醒对于动物生存至关重要，但是大脑坐标的机制从脑干到皮层之间的这些大脑状态之间的切换尚不清楚。神经调节信号传导电路是在睡眠/唤醒和其他情况下的大脑状态切换的重要系统。在电流中提案，我们探讨了这些神经调节剂之一（组织胺）在睡眠和睡眠调节中的作用醒来大脑皮层。尽管组胺长期以来一直被称为促唤醒的神经调节剂与其他人相比，相对理解，因此我们对其细胞和电路机制的理解行动仍处于早期阶段。在这里，我们对睡眠/唤醒涉及的细胞类型进行整体视角电路，询问大脑中最大的非神经元细胞如何参与发送并响应皮质中的组胺能信号。我们旨在解决我们对睡眠/唤醒知识的差距通过发现关键细胞的动力学，组胺能信号传导和星形胶质细胞调节星形胶质细胞中的生物信号系统。我们应用高级光学，电生理和中性操纵技术可以揭示星形胶质细胞如何在皮质中整合神经调节信号电路和神经元的协调人群。我们的主要目标包括：探测细胞生物学组胺激活星形胶质细胞的机制，测试组胺和星形胶质细胞确定其因果关系，并探索星形胶质细胞的机制同步或对神经元活性。