Dissecting and modifying temporal dynamics underlying major depressive disorder

剖析和修改重度抑郁症背后的时间动态

• 批准号: 10085101
• 负责人: Kafui Dzirasa
• 金额: $ 2.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-17 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10085101
• 关键词: 129 Mouse; Administrative Supplement; Amygdaloid structure; Animals; Architecture; Behavior; Behavior assessment; Behavioral; Behavioral Research; Brain; Brain region; Chronic; Chronic stress; Clinical; Complement; Complex; Counseling; Data Analyses; Development; Disease; Electrodes; Electrophysiology (science); Environmental Risk Factor; Exhibits; Experimental Designs; Exposure to; Frequencies; Funding; Genes; Genetic; Grant; Health; Hippocampus (Brain); Human; Implant; Learning; Machine Learning; Major Depressive Disorder; Manuscripts; Measurement; Measures; Mental Depression; Mental disorders; Mentorship; Methods; Molecular Genetics; Mouse Strains; Mus; Neurobiology; Neurodevelopmental Disorder; Neurosciences; Neurosciences Research; Patients; Pattern; Phase; Polysomnography; Prefrontal Cortex; Psychiatrist; Psychiatry; Publications; Publishing; Research; Research Personnel; Research Project Grants; Running; Scientist; Sleep; Sleep Architecture; Sleep Wake Cycle; Sleep disturbances; Social Functioning; Social Interaction; Stress; Structure; Sucrose; Supervision; Tail Suspension; Techniques; Testing; Thalamic structure; Training; Translating; Validation; Work; Writing; autism spectrum disorder; base; career; clinically relevant; cognitive function; common symptom; depression model; disabling symptom; emotional functioning; experience; experimental study; genetic manipulation; in vivo; machine learning algorithm; mouse model; network architecture; neural circuit; neural network; neuronal circuitry; neurophysiology; neuropsychiatric disorder; neuropsychiatry; non rapid eye movement; novel; novel therapeutics; parent grant; preference; rapid eye movement; relating to nervous system; social defeat; spatiotemporal; standard measure; stress tolerance; translational neuroscience

Project Summary of Work The purpose of this administrative supplement application is to provide support for Dr. Alexandra Bey, a psychiatry resident and neuroscience researcher, to expand her opportunities to carry out translational neuroscience research during her clinical training. By conducting the project outlined in this grant, Dr. Bey will gain invaluable experience in new scientific techniques, will study a behavior and its underlying neural dynamics extremely important to neuropsychiatric illnesses, and obtain personalized mentorship that will prepare her for an independent scientific career. To her accomplished skillset in molecular genetics and mouse behavior, she will develop electrophysiology and machine learning techniques in order to advance her ability to study neuronal circuits relevant to neurodevelopmental disorders. Through supervision by Dr. Kafui Dzirasa, Dr. Bey will receive intensive mentorship on experimental design, data analysis, manuscript publication, and grant-writing in order to prepare her to run a research group and compete for independent funding. Additionally, through regular counsel from a committee of preeminent clinician-scientists, Dr. Bey will obtain guidance and support for developing as a psychiatrist-neuroscientist as well as obtain relevant clinical exposure to patients with autism. Dr. Bey and Dr. Dzirasa have developed the following research project to investigate the neural dynamics of sleep. Furthermore, sleep as a behavior is quantifiable, translational, and frequently disrupted in many psychiatric and neurodevelopmental disorders. At present, there is very limited understanding of neural networks underlying sleep architecture. Dr. Bey’s experience with generating and characterizing different genetic mouse models of neuropsychiatric disorders uniquely poise her to advance her skillset to include techniques to truly dissect neural circuits, networks, and their dynamics. Utilizing Dr. Dzirasa’s expertise in in vivo electrophysiology, our collaborator Dr. David Carlson’s expertise in machine learning, we will support Dr. Bey in her efforts to: 1) obtain multisite in vivo electrophysiological recordings in mouse models of neuropsychiatric disease during sleep and wake states, 2) utilize machine-learning algorithms to identify altered neural circuit oscillations contributing to sleep architecture, and 3) extend this work to include a clinically relevant genetic manipulation to examine gene x stress interaction on the dynamics of sleep. Dr. Bey will be a key contributor to the development of each of these experiments and through their conduct, will develop expertise in measuring and understanding neural circuit function which will allow her to advance her career in studying the neurobiological basis of autism.

项目摘要 此行政补充申请的目的是为Alexandra Bey博士提供支持， 精神病学居民和神经科学研究人员，以扩大她进行翻译的机会 神经科学研究在她的临床培训期间。通过在这笔赠款中概述的项目，Bey Will博士 获得新科学技术的宝贵经验，将研究一种行为及其基本神经 动态对神经精神疾病极为重要，并获得个性化心态 为她准备独立的科学生涯。对于她在分子遗传学和小鼠方面成熟的技能 行为，她将开发电生理学和机器学习技术，以提高她的能力 研究与神经发育障碍有关的神经元电路。通过Kafui Dzirasa博士的监督， Bey博士将获得有关实验设计，数据分析，手稿出版和 赠款写作是为了准备她经营一个研究小组并争夺独立资金。 此外，通过杰出临床科学家委员会的定期律师，Bey博士将获得 指导和支持作为精神病医生 - 神经科学家，并获得相关的临床 接触自闭症患者。 Bey博士和Dzirasa博士已经开发了以下研究项目 研究睡眠的神经动力学。此外，作为行为的睡眠是可量化的，翻译的，并且 经常在许多精神病和神经发育障碍中受到干扰。目前，有非常有限的 了解睡眠体系结构的神经网络。 Bey博士在生成和 表征神经精神疾病的不同遗传小鼠模型独特地使她促进她 技能以包括真正剖析神经回路，网络及其动态的技术。利用博士 Dzirasa的体内电生理学专业知识，我们的合作者David Carlson博士的机器专业知识 学习，我们将支持Bey博士的努力：1）在体内获得多站点的电生理记录 睡眠和唤醒状态期间神经精神病的小鼠模型，2）使用机器学习 识别改变导致睡眠体系结构的神经电路振荡改变的算法，3） 工作以包括临床相关的基因操纵，以检查动力学的基因X胁迫相互作用 睡眠。 Bey博士将是每个实验的开发的关键因素，并通过其开发 行为，将发展在衡量和理解神经电路功能方面的专业知识，这将使她能够 在研究自闭症的神经生物学基础上，她的职业生涯促进了职业。