Physiology Core - Interdepartmental Two-photon Imaging Center

生理学核心-跨部门双光子成像中心

• 批准号: 8374450
• 负责人: David Wokosin
• 金额: $ 11.03万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8374450
• 关键词: Alzheimer' s Disease; Area; Brain; Cells; Collaborations; Collection; Communication; Complex; Dendrites; Disease; Drug abuse; Enzymes; Equipment; Faculty; Funding; G Protein-Coupled Receptor Signaling; Grant; Health; Human Resources; Image; Investments; Ion Channel; Life; Membrane; Microscopic; Motion; National Institute of Neurological Disorders and Stroke; Nature; Neurology; Neurons; Neurosciences; Ophthalmology; Optical Methods; Optics; Parkinson Disease; Peripheral Nervous System; Physiology; Property; Publications; Recruitment Activity; Research Personnel; Role; Strategic Planning; Structure; Synapses; Technology; Tissues; Translational Protein Modification; United States National Institutes of Health; Water; Work; base; experience; insight; member; nervous system disorder; neuropsychiatry; postsynaptic; presynaptic; synaptic function; two-photon; voltage

2P Imaging and Dendritic-Synaptic Physiology In order for the brain and peripheral nervous system to work properly, neurons must communicate effectively with one another. This communication is accomplished at specialized structures called synapses. The vast majority of synaptic contacts are made on neuronal dendrites. Synaptic complexes found in dendrites are complex transduction machines created by a partnership between pre- and postsynaptic cells. The dendritic membrane outside of the synaptic specialization is also a highly specialized, dynamic structure that is richly invested with voltage-dependent ion channels, G-protein coupled receptors, signaling enzymes, translational and protein processing machinery. Fundamental insights into the roles of dendrites in health and disease are emerging from our ability to visualize these microscopic regions dynamically in living tissue. NU is rapidly becoming a world center in the study of dendrites and synaptic function. The NU group was nucleated by the recruitment of Drs. Nelson Spruston and Catherine Wooley, internationally recognized leaders in the study of neuronal dendrites. In 2001, Dr. James Surmeier was recruited to the Chair of the Physiology Department at FSM. Having a well-established reputation for the study of neuromodulatory mechanisms that are critical to dendritic function in neurons, he put in motion a strategic plan to dramatically expand the group of neuroscientists working in this area at NU. This decision was predicated upon 1) existing strengths in this area, 2) the recognition that this was an emerging area of neuroscience and 3) the conviction that a wide array of major neurological disorders - Parkinson's disease, Alzheimer's disease, neuropsychiatric disorders, and drug abuse - were likely to be primarily disorders of dendrites and synaptic function. With the recruitment of twelve new faculty members into this area in the last three years, this group has achieved a critical mass. Even though the recruitment has focused heavily on junior investigators (because this is an emerging area of neuroscience), the group is already very well funded by NIH, receiving roughly $12M in 2004-05, of which $XM is derived from NINDS. This figure is sure to grow as many of the young recruits with 2P expertise (e.g., P. Osten, J. Waters, G. Shepherd) are submitting their first grants to NINDS this year. Collectively, this group represents one of the largest and most experienced collections of physiologists pursuing dendritic and synaptic physiology in the world (Table 1A). Most are experienced electrophysiologists, and several are experts at electrical recording from dendrites (Spruston, Maccaferri, Martina, Waters, Osten). Several are experts at using optical methods for studying dendritic properties (Hockberger, Spruston, Grutzendler, Shepherd, Penzes, Waters, Osten). Others are currently developing this expertise (Surmeier, Bevan, Mintz, Martina, Singer) with publications beginning to appear in this area (e.g., Surmeier's lab: Day et al., Nature Neuroscience, Feb. 2006). Most of the investigators are in the same department (Physiology) where they have the opportunity to interact with one another on a daily basis. Most of those who are in the Ophthalmology and Neurology departments have adjacent labs. Surmeier, Miller, Rao and Bevan are in one large open lab space. The contiguity of most of the participating faculty creates a unique opportunity for crossfertilization of ideas and collaborations. Because each of these investigators is posing important questions about dendrites and synapses, a clear obstacle to maximizing the yield on the NINDS and NU investment in them is their limited access to non-linear optical technology. In the last three years, NU has taken steps to correct this limitation by making a major investment in space, equipment and personnel. This proposal aims to build upon this investment to make this technology available to investigators throughout NU.

2 P成像和树突-突触生理学 为了使大脑和周围神经系统正常工作，神经元必须有效地交流 彼此联系。这种交流是在称为突触的特殊结构中完成的。绝大多数 突触接触是在神经元树突上进行的。在树突中发现的突触复合体是复杂的 由突触前和突触后细胞之间的伙伴关系创建的转导机器。树突膜 在突触特化之外，还有一个高度特化的动态结构， 电压依赖性离子通道、G蛋白偶联受体、信号传导酶、翻译和蛋白质加工 机械.树突在健康和疾病中的作用的基本见解正在从我们的 能够动态地可视化活组织中的这些微观区域。 NU正在迅速成为树突和突触功能研究的世界中心。NU集团是 由纳尔逊斯普鲁斯顿博士和凯瑟琳伍利，国际公认的领导人， 在神经树突的研究中。2001年，James Surmeier博士被聘为生理学系主任。 在FSM的部门。在神经调节机制的研究方面享有盛誉， 对于神经元中的树突功能至关重要，他启动了一项战略计划， 神经科学家在这个领域工作这一决定是基于1）这一领域的现有优势， 2)认识到这是神经科学的一个新兴领域，3）相信广泛的 主要神经系统疾病-帕金森病、阿尔茨海默病、神经精神疾病和药物 滥用-可能主要是树突和突触功能障碍。招募了12名 在过去的三年里，新的教员进入这个领域，这个群体已经达到了临界质量。即使 招聘主要集中在初级研究人员（因为这是神经科学的一个新兴领域）， 该小组已经得到了美国国立卫生研究院的充分资助，在2004- 2005年收到了大约1200万美元，其中XM美元来自 NINDS。这一数字肯定会随着拥有2 P专业知识的年轻新兵（例如，P. Osten，J.沃茨， G. Shepherd）今年向NINDS提交了他们的第一笔赠款。 总的来说，这个小组代表了最大和最有经验的生理学家的集合之一 在世界上从事树突和突触生理学的研究（表1A）。大多数是经验丰富的电生理学家， 有几位是从树突进行电记录的专家（Spruston，Maccaferri，Martina，沃茨， Osten）。有几位专家擅长使用光学方法研究树枝状特性（Hockberger，Spruston， Grutzendler，Shepherd，Penzes，沃茨，Osten）.其他人目前正在开发这种专门知识（Surmeier， Bevan，Mintz，Martina，Singer），该领域的出版物开始出现（例如，Surmeier的实验室：白天 例如，Nature Neuroscience，2006年2月）。大多数研究者在同一个部门（生理学） 在那里，他们有机会每天互相交流。大多数人都在 眼科和神经科有相邻的实验室。苏迈尔、米勒、拉奥和贝文合二为一 大型开放式实验室大多数参与教师的邻近性为交叉施肥创造了独特的机会 of ideas思路and collaborations合作. 因为这些研究者都提出了关于树突和突触的重要问题， 最大限度地提高NINDS和NU投资收益的障碍是他们有限的访问， 非线性光学技术。在过去的三年里，NU已经采取措施纠正这一限制， 在空间、设备和人员方面的重大投资。这项建议旨在利用这项投资， 这项技术可以提供给整个NU的调查人员。