Physiology Core - Interdepartmental Two-photon Imaging Center

2P成像与树突-突触生理学 为了让大脑和周围神经系统正常工作，神经元必须进行有效的沟通 彼此之间的关系。这种交流是在称为突触的特殊结构中完成的。绝大多数人 突触的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 由突触前细胞和突触后细胞合作创造的转导机器。树突膜 在突触专门化之外，还有一个高度专业化的、动态的结构，它与 电压依赖性离子通道、G蛋白偶联受体、信号酶、翻译和蛋白质加工 机械设备。对于树突在健康和疾病中的作用的基本见解正在从我们的 在活组织中动态显示这些微观区域的能力。 北大正在迅速成为树突和突触功能研究的世界中心。怒族是 由纳尔逊·斯普鲁斯顿博士和凯瑟琳·伍利博士的招聘而成，他们是国际公认的领导者 在神经元树突的研究中。2001年，詹姆斯·苏梅尔博士被聘为生理学主任 密克罗尼西亚联邦安全局。在研究神经调节机制方面享有盛誉， 对神经元的树突状细胞功能至关重要，他启动了一项战略计划，大幅扩大 努尔大学研究这一领域的神经学家。这一决定是基于1)这一领域现有的优势， 2)认识到这是神经科学的一个新兴领域；3)坚信 主要神经疾病-帕金森氏病、阿尔茨海默病、神经精神障碍和药物 滥用-可能主要是树突和突触功能的障碍。招募了12个人 在过去的三年里，这一群体已经达到了临界值。即使 招聘主要集中在初级调查人员(因为这是神经科学的一个新兴领域)， NIH已经为该组织提供了非常充足的资金，在2004-05年度获得了大约1200万美元的资金，其中XM美元来自 NINDS。这一数字肯定会增长，因为许多拥有2P专业知识的年轻新人(例如P.Osten、J.Waters、 G·谢泼德)今年向NINDS提交了他们的第一笔赠款。 总体而言，这一群体代表了规模最大、经验最丰富的生理学家群体之一 世界上正在研究树突和突触的生理学(表1A)。大多数都是经验丰富的电生理学家， 还有几个是树枝状岩石(Spruston，Maccaferri，Martina，Waters， 奥斯汀)。一些人是使用光学方法研究树枝状特性的专家(Hockberger，Spruston， 格鲁特曾德勒、谢泼德、彭泽斯、沃特斯、奥斯汀)。其他人目前正在开发这种专业知识(Surmeier， Bevan，Mintz，Martina，Singer)，出版物开始在这一领域出现(例如，Surmeier的实验室：DAY 等人，自然神经科学，2006年2月)。大多数研究人员都在同一个系(生理学) 在那里他们有机会在每天的基础上相互互动。大多数在美国的人 眼科和神经科都有邻近的实验室。苏梅尔、米勒、拉奥和贝文合二为一 宽敞的开放实验室空间。大多数参与的教职人员的毗邻创造了一个独特的交叉受精机会 点子和合作。 因为每个研究人员都提出了关于树突和突触的重要问题，一个明确的 NINDS和NU投资最大化收益的障碍是他们获得的机会有限 非线性光学技术。在过去的三年里，NU采取措施纠正这一限制，制定了一项 在空间、设备和人员方面的重大投资。这项提议旨在建立在这一投资的基础上 这项技术可供NU各地的调查人员使用。

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.