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：
10159967
负责人：
Kira Poskanzer
金额：
$ 43.48万
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/10159967
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

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.

睡眠和觉醒对于动物的生存至关重要，但大脑协调的机制从脑干到皮质的这些大脑状态之间的切换仍不清楚。无论是在睡眠/清醒状态还是在当前情况下，电路都是大脑状态切换的重要系统。根据提议，我们探讨了其中一种神经调节剂——组胺——在调节睡眠和睡眠中的作用。尽管组胺长期以来被认为是一种促进唤醒的神经调节剂，但它与其他相比，我们对它的研究相对较少，因此我们对其细胞和电路机制的了解行动仍处于早期阶段，我们对参与睡眠/觉醒的细胞类型进行整体视角。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信号以及对皮质中的组胺信号做出反应我们的目标是解决我们在睡眠/觉醒方面的知识空白。通过发现关键细胞来研究神经回路的动力学、组胺能信号传导和星形胶质细胞调节我们在星形胶质细胞中应用先进的光学、电生理和神经信号系统。操纵技术揭示星形胶质细胞如何整合皮质中的神经调节信号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，测试组胺和星形胶质细胞的时空动态星形胶质细胞以确定其因果关系，并探索星形胶质细胞可能的机制同步或去同步神经活动。