A multiphoton system that allows simultaneous multiphoton imaging and 3D optical stimulation

允许同时进行多光子成像和 3D 光学刺激的多光子系统

• 批准号: 10282627
• 负责人: ZHIPING P. PANG
• 金额: $ 60万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-11 至 2022-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10282627
• 关键词: 3-Dimensional; Advisory Committees; Behavior Control; Biophotonics; Brain; Brain Diseases; Calcium; Child Health; Complex; Consultations; Contract Services; Development; Dopamine; Ensure; Experimental Designs; Fright; Functional Imaging; Funding; G-Protein-Coupled Receptors; Gilles de la Tourette syndrome; Health Sciences; Image; Institutes; Laboratory Research; Lasers; Maintenance; Mediating; Mental Depression; Mental disorders; Microscope; Molecular; National Institute of Mental Health; Neurons; Neurosciences; New Brunswick; New Jersey; Opsin; Optics; Play; Postdoctoral Fellow; Principal Investigator; Reporter; Research; Research Personnel; Research Support; Role; Sampling; Schools; Science; Speed; Synapses; System; Technology; Tissue imaging; Training; United States National Institutes of Health; Wood material; autism spectrum disorder; brain behavior; cell type; cost; instrument; instrumentation; medical schools; member; multiphoton imaging; multiphoton microscopy; neural network; novel; novel therapeutics; optical sensor; optogenetics; relating to nervous system; transmission process; two-photon; voltage

Abstract/Project Summary In this project, we request funds to acquire an upright Bruker NeuraLight 3D spatial laser modulator (SLM) Ultima multiphoton microscope to enable simultaneous multiphoton imaging and 3D holographic optical stimulation. The instrument will allow simultaneous deep brain, decoupled, two-photon functional imaging of neuronal activity and SLM holographic optogenetic stimulations to study and understand neural connectivity and how neural networks control behavior. The instrument will be housed at the Child Health Institute of New Jersey (CHINJ) at Rutgers Robert Wood Johnson Medical School (RWJMS) to support research in unraveling the molecular, synaptic, and cellular mechanisms underlying mental disorders in a cell type- and circuity-specific manner. This instrument will be the first of its kind on the Rutgers Biomedical and Health Sciences (RBHS) and Rutgers New Brunswick/Piscataway campuses and will fill a critical void in available technologies to multiple investigators funded by NIMH at Rutgers. The core users of the system will be prioritized to NIMH-funded research laboratories with expertise in developing novel optical sensors, and studying fear, depression, and autism and Tourette syndromes, but will also be available for use by other NIH-funded researchers. This cutting-edge instrumentation will meet a critical need in the dramatically increased demand for deep tissue imaging with cell type and circuitry- specific optogenetic manipulations, essential for understanding complex brain disorders and behaviors, which cannot be met by any other systems currently available on campus. Recent developments in optics technologies, specific opsins and genetically encoded neuronal activity reporters including GCaMPs (calcium), Voltron & ASAP (voltage), dLight or GRAB-DA (dopamine), as well as Reporters for Transmission mediated by GPCRs (RTGRs) which we are currently developing, have made these research paradigms possible. Importantly, we have obtained strong commitments from the CHINJ, Rutgers-RWJMS, and Rutgers-School of Arts and Sciences for this application to acquire this state-of-the-art upright multiphoton microscopy system, including designated space, funding for additional instrumentation costs, and long-term support for an extended service contract and maintenance for the system. The principal investigator and a senior lab research associate, along with local technical experts, will be responsible for all user training and routine daily maintenance, as well as providing user assistance, consultation on experimental design and advice on system configuration and optimal system use. An advisory committee composed of members with strong expertise in biophotonics has been formed to ensure proper and efficient use of the facility. We anticipate that the addition of this system will not only greatly strengthen current NIMH-funded projects but will also allow users to explore new questions previously not addressable due to the absence of a platform able to image deeply into samples with high speed neuronal activity manipulations. Therefore, this instrument will play a critical role in promoting new discoveries in neuroscience and help towards devising novel therapeutics for treating mental disorders.

摘要/项目摘要 在这个项目中，我们要求资金购买立式Bruker NeuraLight 3D空间激光调制器(SLM)Ultima 多光子显微镜，可同时实现多光子成像和3D全息光学刺激。 该仪器将允许同时对大脑深处的神经元活动进行去耦合的双光子功能成像 和SLM全息光发生刺激来研究和了解神经连接以及神经如何 网络控制行为。该仪器将放置在新泽西州儿童健康研究所(CHINJ)，地址为 罗格斯大学罗伯特·伍德·约翰逊医学院(RWJMS)支持研究解开分子， 突触和细胞机制以细胞类型和环路特有的方式潜伏在精神障碍之下。这 该仪器将是罗格斯大学生物医学和健康科学(RBHS)和罗格斯大学新实验室的首个此类仪器 Brunswick/Piscataway校园，将填补可供多名调查人员使用的技术方面的关键空白 由罗格斯大学的NIMH资助。该系统的核心用户将优先进入NIMH资助的研究实验室 在开发新型光学传感器以及研究恐惧、抑郁、自闭症和抽动障碍方面拥有专业知识 但也将可供NIH资助的其他研究人员使用。这种尖端的仪器 将满足细胞类型和电路对深层组织成像需求急剧增加的关键需求- 特定的光遗传操作，对于理解复杂的大脑障碍和行为至关重要，这 不能被校园中当前可用的任何其他系统所满足。光学技术的最新发展， 特定的视蛋白和遗传编码的神经元活动报告，包括GCaMPs(钙)、Voltron和ASAP (电压)，dLight或Grab-DA(多巴胺)，以及GPCRs介导的传输报告(RTGRs) 我们目前正在开发的，使这些研究范式成为可能。重要的是，我们有 得到了CHINJ、罗格斯-RWJMS和罗格斯-艺术与科学学院的大力支持 此应用程序获取这一最先进的立式多光子显微镜系统，包括指定的 空间、额外仪器费用的资金以及对延长服务合同和 系统的维护。首席调查员和一名高级实验室研究助理，以及当地 技术专家，将负责所有用户培训和日常维护，以及为用户提供 就实验设计提供协助、咨询，并就系统配置和最佳系统使用提供建议。 一个由在生物光子学方面拥有强大专业知识的成员组成的咨询委员会已经成立，以确保 适当和高效地使用设施。我们预计，这一系统的增加不仅将大大 加强目前由NIMH资助的项目，但也将允许用户探索以前没有 由于缺乏能够深入成像到具有高速神经元活动的样本的平台而可寻址 操纵。因此，这一仪器将在促进神经科学的新发现方面发挥关键作用。 并有助于设计治疗精神障碍的新疗法。