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Role of orexin/hypocretin circuit in anesthesia and analgesia

食欲素/下丘脑分泌素回路在麻醉和镇痛中的作用

基本信息

批准号：
10651642
负责人：
Wei Zhou
金额：
$ 19.91万
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：
2020-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10651642
关键词：
3-Dimensional Absence of pain sensation Address Affect Agitation Alzheimer&apos s Disease Anesthesia and Analgesia Anesthesia procedures Anesthetics Animal Behavior Animal Testing Animals Arousal Biological Assay Brain Brain region Calcium California Cardiovascular system Cataplexy Chemicals Dedications Delirium Development Electric Stimulation Electroencephalography Emotions Equipment Exhibits Formalin Tests Foundations Funding Future Genetic Goals Habenula Homeostasis Hypothalamic structure Institution Isoflurane Knowledge Lateral Light Link Maps Mental Depression Mentors Microscopy Midbrain structure Modern Medicine Monitor Mus Muscle Tonus Muscular Atrophy Narcolepsy Neuroanatomy Neurons Nociception Operative Surgical Procedures Opioid Pain Pain Threshold Pain management Pathogenesis Patient Care Patients Pattern Perioperative Care Physicians Recovery Regulation Reporting Research Rewards Risk Rodent Role San Francisco Scientist Site Sleep Sleep Architecture Sleep Fragmentations Solid Speed Spinal Cord Spinal cord posterior horn Stress Structure Surface System Techniques Technology Testing Time Training Transgenic Mice Universities Visualization Volatilization Wakefulness Work acute stress aging brain antinociception basal forebrain biological adaptation to stress career career development clinical practice dopaminergic neuron experience genetic approach hypocretin in vivo calcium imaging in vivo imaging midbrain central gray substance multidisciplinary nerve supply neural neural circuit neural network neuropsychiatry neurotoxicity novel optogenetics pain behavior pain relief professor respiratory sleep regulation tool voltage

项目摘要

Project Summary/Abstract With the long-term research goal of advancing anesthesia through developing new tools and techniques for better anesthetic management and pain control, the candidate focuses his research on elucidating the mechanisms underlying anesthesia, in particular, the role of hypothalamic orexin (Ox) circuit in anesthesia and analgesia. How anesthetics interact with brain neural network is still poorly understood. The Ox circuit is considered to be a master regulator in sleep/wakefulness. The candidate's recent work showed that activation of Ox neurons with chemogenetic approach facilitates emergence from isoflurane anesthesia and induces analgesia. Building upon these findings, he proposes to apply optogenetics to specifically activate subsets of Ox projections to address the underlying mechanisms. The candidate started with mapping the basic neuroanatomy of the Ox projections in the mouse brain. In his preliminary work, he mapped out three-dimensional Ox projections using both confocal and lightsheet microscopy and identified three interesting regions he will focus on in this proposal. In aim 1, he will test the hypothesis that Ox neurons regulate arousal state during anesthesia via their projections to basal forebrain (BF) and lateral habenula (LHb). In aim 2, he plans to test the hypothesis that Ox projections to periaqueductal gray (PAG) contributes to analgesia. While manipulating neuronal activities with optogenetic tools, the candidate will record electroencephalogram (EEG), image in vivo neural calcium activities, and test the animal's behavior related to arousal state or pain. The proposed work will lead to the identification of novel roles of different subsets of Ox projections in anesthesia-related arousal and pain control. The candidate is currently an Assistant Professor in the Department of Anesthesia and Perioperative Care at the University of California San Francisco (UCSF). His career goal is to become an independent physician scientist dedicated to understanding the mechanisms governing anesthesia and bring patient care to the next level with safer and more efficient anesthesia. The candidate has outstanding institutional support with 75% protected research time, lab and office space, administrative support, and department funding for a technician and selected equipment. UCSF is a world-class institute and the candidate has a multidisciplinary mentoring team to guide his career development. Additionally, he has an extensive didactic plan to take advanced training in the next few years to further build a solid foundation for his expertise in the research on the role of neural circuits in anesthesia and analgesia.

项目摘要/摘要长期的研究目标是通过开发新的工具和技术来促进麻醉更好的麻醉管理和疼痛控制，候选人的研究重点是阐明麻醉的机制，特别是下丘脑增食欲素(Ox)环路在麻醉和麻醉中的作用止痛药。麻醉剂如何与大脑神经网络相互作用仍然知之甚少。Ox电路是被认为是睡眠/清醒状态的主要调节者。候选人最近的研究表明，激活应用化学遗传学方法诱导Ox神经元从异氟醚麻醉中苏醒止痛药。在这些发现的基础上，他建议应用光遗传学来特定地激活Ox的亚群针对潜在机制的预测。候选人从绘制基本的神经解剖学开始小鼠大脑中的Ox投射。在他的前期工作中，他绘制了三维公牛使用共焦显微镜和光片显微镜进行投影，并确定了他将关注的三个有趣的区域在这项提案中。在目标1中，他将测试Ox神经元在麻醉过程中调节觉醒状态的假设通过向基底前脑(BF)和外侧缰核(LHb)投射。在《目标2》中，他计划检验这一假说 Ox投射至中脑导水管周围灰质(PAG)参与镇痛。当操控神经元活动时利用光遗传工具，考生将记录脑电(EEG)，图像中的活体神经钙活动，并测试动物与唤醒状态或疼痛相关的行为。拟议的工作将导致识别Ox投射的不同子集在麻醉相关觉醒和疼痛控制中的新作用。候选人目前是麻省理工学院麻醉和围手术期护理系的助理教授。加州大学旧金山分校(UCSF)。他的职业目标是成为一名独立的内科科学家致力于了解麻醉的管理机制，并将患者护理提高到新的水平更安全、更有效的麻醉。候选人拥有杰出的机构支持，75%的人受到保护技术人员和选定人员的研究时间、实验室和办公空间、行政支持和部门资金设备。加州大学旧金山分校是一所世界级的学院，候选人有一个多学科的指导团队来指导他的职业发展。此外，他还有一个广泛的教学计划，将在接下来的几年里接受高级培训几年来，他为自己在麻醉中神经回路作用的研究奠定了坚实的基础和止痛药。