Non-Neuronal Sleep/Wake Control in Cortex

皮层的非神经元睡眠/唤醒控制

• 批准号: 10591515
• 负责人: GRAEME W DAVIS
• 金额: $ 34.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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/10591515
• 关键词: Acetylcholine; Address; Animal Behavior; Animals; Area; Astrocytes; Basic Science; Biological; Brain; Brain Stem; Calcium; Cells; Cerebral cortex; Dopamine; Electrophysiology (science); Equilibrium; Exhibits; Fiber; Future; Glutamates; Goals; Health; Histamine; Histamine H1 Receptors; Histamine Receptor; Human; Image; Knowledge; Maps; Measures; Mental disorders; Metabolism; Modeling; Modernization; Molecular; Morphology; 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; neural circuit; neuronal circuitry; neuroregulation; neurotransmission; receptor expression; response; sleep regulation; spatiotemporal; targeted treatment; tool; two-photon

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.

睡眠和清醒对动物的生存至关重要，但大脑协调的机制 从脑干到大脑皮层，这些大脑状态之间的转换仍不清楚。神经调节信号 无论是在睡眠/清醒状态下还是在其他环境中，回路都是大脑状态切换的基本系统。在当前 提案中，我们探讨了其中一种神经调节剂--组胺--在调节睡眠和 在大脑皮层苏醒。尽管组胺长期以来一直被认为是一种促进觉醒的神经调节剂，但它 与其他人相比，对它的研究相对较少，所以我们对其细胞和电路机制的了解 行动仍处于早期阶段。在这里，我们对睡眠/清醒过程中涉及的细胞类型进行整体观察 电路，并询问大脑中最大的一类非神经细胞--星形胶质细胞是如何参与发送 以及对大脑皮层中的组胺能信号做出反应。我们的目标是解决我们在睡眠/清醒知识方面的差距 揭示关键细胞对神经回路的动力学、组胺能信号和星形胶质细胞调节 星形胶质细胞中的生物信号系统。我们应用先进的光学、电生理和神经技术 揭示星形胶质细胞如何整合大脑皮层神经调制信号的操作技术 神经回路和协调的神经元群体。我们的主要目标包括：探索细胞生物学 组胺激活星形胶质细胞的机制，测试组胺和 以确定它们之间的因果关系，并探索星形胶质细胞可能 同步化或去同步化神经元活动。