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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：
10186780
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/10186780
关键词：
3-Dimensional Absence of pain sensation Acute 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 Delirium Development Electric Stimulation Electroencephalogram Emotions Equipment Exhibits Formalin Tests Foundations Funding Future Goals Habenula Hypothalamic structure Institutes Isoflurane Knowledge Lateral 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 Fragmentations Solid Speed Spinal Cord Spinal cord posterior horn Stress Structure Suggestion Surface System Techniques Technology Testing Time Training Transgenic Mice Universities Wakefulness Work aging brain basal forebrain base career career development clinical practice experience hypocretin in vivo calcium imaging in vivo imaging midbrain central gray substance multidisciplinary nerve supply neural circuit neural network neuropsychiatry neurotoxicity novel optogenetics pain behavior pain relief professor relating to nervous system respiratory 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.

项目总结/文摘