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.

项目工作总结 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员，以扩大她的机会，进行翻译 神经科学研究在她的临床训练。通过进行这项资助中概述的项目，贝博士将 在新的科学技术中获得宝贵的经验，将研究行为及其潜在的神经 动力学对神经精神疾病非常重要，并获得个性化的指导， 为她独立的科学生涯做准备。她在分子遗传学和小鼠遗传学方面的造诣 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相关的神经回路。在Kafui Donghasa博士的监督下， 博士Bey将在实验设计、数据分析、手稿出版和 为了准备她运行一个研究小组，并争取独立的资金。 此外，通过杰出的临床科学家委员会的定期顾问，贝博士将获得 指导和支持发展为精神病学家，神经科学家，以及获得相关的临床 接触自闭症患者。Bey博士和Djanasa博士开发了以下研究项目， 研究睡眠的神经动力学。此外，睡眠作为一种行为是可量化的，转化的， 在许多精神和神经发育障碍中经常中断。目前， 了解睡眠结构背后的神经网络。贝伊博士的经验与生成和 描述不同的神经精神疾病遗传小鼠模型，使她能够独特地推动她的研究。 技能包括真正剖析神经回路，网络及其动态的技术。利用博士 我们的合作者大卫卡尔森博士在机器方面的专长 学习，我们将支持贝博士在她的努力：1）获得多部位在体内电生理记录， 睡眠和清醒状态下的神经精神疾病小鼠模型，2）利用机器学习 算法，以识别改变的神经回路振荡有助于睡眠结构，和3）扩展这一点 工作，包括临床相关的遗传操作，以检查基因x应力相互作用的动力学 睡眠。贝伊博士将是这些实验的发展的关键贡献者，并通过他们的 行为，将发展测量和理解神经回路功能的专业知识，这将使她 在研究自闭症的神经生物学基础方面推进她的事业。