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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

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.

睡眠和清醒对动物的生存至关重要，但大脑协调的机制