Multi-photon laser scanning microscope

描述（由申请人提供）：本提案的目标是购买/获取和实施一台双光子显微镜，该显微镜将主要用于加强赖特州立大学的神经科学研究，并允许主要研究人员进行研究，否则他们将无法完成。我们已经组建了一个由非常有成就的研究人员组成的团队，他们将构成所要求的仪器的主要用户，并且所有这些都是NIH资助赠款（R 01）的PI。弗朗西斯科阿尔瓦雷斯博士将使用所要求的仪器研究Renshaw细胞在发育中的脊髓中的生成和功能作用。这项研究对成年人脊髓损伤后神经元的运动发育、重构和功能恢复具有广泛的意义。弗朗西斯科Alvarez-Leefman博士将利用显微镜了解神经元和神经胶质细胞中细胞体积控制的细胞和分子机制。Robert Fyffe博士将利用显微镜研究活动改变或轴突损伤后表面膜离子通道定位的动力学，该项目也对脊髓/神经损伤和恢复领域产生影响。Robert Putnam博士将使用所要求的仪器研究细胞内Ca和pH在脑干神经元树突化学敏感信号传导中的作用。对中枢化学敏感信号的更深入理解将为旨在改变中枢换气不足综合征、SIDS和睡眠呼吸暂停等疾病的呼吸驱动的治疗开辟新的靶点。该仪器将被安置在最近创建的综合神经科学中心的核心设施中并得到充分支持，除了这四个主要用户外，其他工作人员/次要用户/初级研究者将有机会使用该仪器进行细胞和分子研究。基于我们目前的专业知识以及我们与NIH的Michael O 'Donovan博士的合作（他邀请Alvarez博士在NIH使用双光子显微镜一个月），我们相信我们将掌握双光子显微镜的使用，并能够充分发挥其潜力。双光子显微镜将增强赖特州立大学的成像核心设施，该设施目前拥有两台共聚焦显微镜和一台透射电子显微镜，所有这些都与离线图像分析工作站联网。将获得的技术专长将用于进一步推进WSU的其他研究工作。公共卫生相关性：双光子显微镜将增强赖特州立大学的神经科学核心，并促进最先进的科学研究。这里提出的研究将充分利用这一工具，从而了解与健康和疾病或损伤条件下的神经系统功能高度相关的神经生理学和神经病理学机制。

DESCRIPTION (provided by applicant): The goal of this proposal is to purchase/acquire and implement a Two-photon microscope which will primarily be utilized to strengthen the neuroscience research at Wright State, and permit key investigators to perform studies they would otherwise be unable to accomplish. We have assembled a team of highly accomplished researchers who will constitute the major users of the requested instrument and all of which are PIs on NIH funded grants (R01s). Dr. Francisco Alvarez will use the requested instrument to study Generation and functional role of Renshaw cells in the developing spinal cord. This study has broad implications on motor development and reconfiguration and recovery of function of neurons in adults after spinal cord injuries that disrupt these intraspinal circuits. Dr. Francisco Alvarez-Leefman will utilize the microscope to understand the cellular and molecular mechanisms underlying cell volume control in neurons and glial cells. Dr. Robert Fyffe will utilize the microscope to investigate the dynamics of surface membrane ion channel localization following altered activity or axonal injury, a project that also has implications in the field of spinal cord/nerve injury and recovery. Dr. Robert Putnam will use the requested instrument to study the role of Intracellular Ca and pH in chemosensitive signaling in dendrites of brainstem neurons. A greater understanding of central chemosensitive signaling will open new targets for treatments aimed at altering respiratory drive in such disorders as central hypoventilation syndrome, SIDS, and sleep apnea. The instrument will be housed and fully supported in a core facility in the recently created Comprehensive Neuroscience Center, where, in addition to these four major users, there will be opportunity for the instrument to be used by additional staff/Minor users/ Junior Investigators for cellular and molecular studies. Based on our current expertise as well as our collaboration with Dr Michael O'Donovan at NIH (who has invited Dr. Alvarez for a month to use a two-photon microscope at NIH) we believe that we will master the use of the Two-photon microscope and will be able to make the most of its potential. A Two-photon microscope will enhance the Imaging Core Facility at Wright State which currently houses two confocal microscopes and a transmission electron microscope, all networked to off-line image analysis workstations. The technical expertise to be gained will be utilized to further advance other research endeavors at WSU. PUBLIC HEALTH RELEVANCE: A Two-Photon Microscope will enhance the Neuroscience core at Wright State University and promote state- of-the art scientific research. The research proposed here will make use of this instrument to its full capacity, leading to an understanding of both neurophysiologic and neuropathologic mechanisms of high relevance to nervous system function in health and disease or injury conditions.