Non-Neuronal Sleep/Wake Control in Cortex

皮层的非神经元睡眠/唤醒控制

• 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
• 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

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 这些大脑状态之间的转换，从脑干到皮层，仍然不清楚。神经调节信号 无论是在睡眠/清醒还是在其他情况下，回路都是大脑状态转换的基本系统。在当前 我们探讨了这些神经调节剂之一-组胺-在睡眠调节中的作用， 在大脑皮层中醒来。尽管组胺长期以来被认为是一种促进觉醒的神经调节剂， 与其他人相比，相对来说研究不足，所以我们对其细胞和电路机制的理解， 行动仍处于初期阶段。在这里，我们对睡眠/觉醒中涉及的细胞类型进行了全面的分析。 电路，并询问大脑中最大的一类非神经元细胞，星形胶质细胞，如何参与发送 并对皮质中的组胺能信号做出反应。我们的目标是解决我们对睡眠/觉醒知识的差距 通过揭示关键细胞的神经回路的动力学、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 操作技术，以揭示星形胶质细胞如何整合皮质神经调节信号， 电路和协调神经元群体。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，测试组胺的时空动态， 星形胶质细胞，以确定其因果关系，并探讨星形胶质细胞可能 使神经元活动同步或去同步化。