Physiology Core - Interdepartmental Two-photon Imaging Center

生理学核心-跨部门双光子成像中心

基本信息

批准号：
7408920
负责人：
David Wokosin
金额：
$ 9.49万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7408920
关键词：
AMD3100 AMPA Receptors Acoustics Action Potentials Acute Address Adolescent Adult Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Analgesics Anesthesia procedures Animal Model Animals Apical Apolipoprotein E Archives Area Astrocytes Atrophic Automation Axon Back Back Pain Ballistics Be++ element Behavior Behavioral Beryllium Biological Biological Assay Biophotonics Blocking Antibodies Brain Brain imaging CCL2 gene CXCR4 gene Calcium Calcium Signaling Caliber Calibration Cancer Center Support Grant Cells Cellular biology Characteristics Charge Chemistry Chicago Chromosome Pairing Chronic Clinical Code Collaborations Collection Color Commit Communication Communities Complement Complex Computer Simulation Computer software Computers Condition Conflict (Psychology)Confocal Microscopy Consult Control Animal Core Facility Count Coupling Cytoplasmic Granules Daily Data Data Analyses Defect Dendrites Dendritic Spines Depth Detection Development Direct Costs Discipline Disease Distal Documentation Dose Drug abuse Dyes Electrodes Electrophysiology (science)Embryo Ensure Environment Enzymes Equation Equipment Estradiol Estrogens Event Excitatory Synapse Exocytosis Extracellular Matrix Proteins Facility Construction Funding Category Faculty Failure Family Feedback Female Figs - dietary Fire - disasters Fluorescence Fluorochrome Functional Imaging Funding Future G Protein-Coupled Receptor Signaling Generations Genetic GluR2 subunit AMPA receptor Glutamate Receptor Glutamates Goals Grant Green Fluorescent Proteins Hand Head Health Hippocampus (Brain)Hour Housing Human Human Resources Image Image Analysis Immersion Investigative Technique Immigration Immune response In Vitro Individual Inflammation Inflammatory Inflammatory Response Injection of therapeutic agent Injury Institutes Integrins Interleukins Interneurons Investments Ion Channel Knockout Mice Knowledge Label Laboratories Language Lasers Lateral Lead Learning Left Letters Life Ligands Link Localized Location Maintenance Manuals Measures Medial Mediating Membrane Methods Microglia Microscope Microscopic Microscopy Modeling Modification Molecular Monitor Morphologic artifacts Morphology Motion Motor Neurons Movement Mus N-Methyl-D-Aspartate Receptors N-Methylaspartate NR1 gene Nature Neonatal Neurology Neurons Neurosciences Nitrogen Noise Numbers Operative Surgical Procedures Ophthalmology Optical Methods Optics Oregon Output Pain Paper Parkinson Disease Participant Patients Pattern Pediatrics Penetration Perforant Pathway Performance Peripheral Peripheral Nervous System Peripheral nerve injury Pharmaceutical Preparations Phenotype Photobleaching Photons Phototoxicity Physiologic pulse Physiological Physiology Play Pliability Positioning Attribute Predisposition Prefrontal Cortex Preparation Presynaptic Terminals Price Principal Investigator Probability Problem Solving Process Production Programmed Learning Property Protocols documentation Publications Pulse taking Pump Pupil Purpose Pyramidal Cells RNA Interference Range Rate Rattus Recording of previous events Recruitment Activity Regulation Research Research Infrastructure Research Personnel Research Project Grants Research Project Summaries Resistance Resolution Retina Retinal Rodent Role Rotation Running Safety Sampling Sapphire Scanning Schedule Seizures Series Services Short-Term Memory Signal Transduction Signaling Molecule Site Slice Slow-Twitch Muscle Fibers Software Engineering Solutions Source Source Code Spinal Spinal Cord Staging Stem cells Stimulus Strategic Planning Stromal Cell-Derived Factor 1 Structure Students Supervision Surface Synapses Synaptic Transmission System Systems Integration Techniques Technology Testing Tetrodotoxin Thalamic structure Thick Thinking Time Tissues Training Training Support Transgenic Mice Transgenic Model Translational Protein Modification Trees United States National Institutes of Health Universities Up-Regulation Update Upper arm Variant Vertebral column Vesicle Visual Water Week Width Wisconsin Work attenuation awake base brain tissue cell behavior cell motility cellular imaging charge coupled device camera chemokine chemokine receptor chronic pain concept cost cytokine data acquisition day density dentate gyrus design desire detector experience extracellular fluorophore granule cell hippocampal pyramidal neuron human NR1 protein human study human subject improved in vivo insight interest lens light emission mature animal member migration monocyte chemoattractant protein 1 receptor mouse model nerve stem cell nervous system disorder nestin protein neural circuit neuroblast neuronal cell body neurophysiology neuropsychiatry novel olfactory bulb patch clamp postnatal postsynaptic pressure presynaptic prevent progenitor programs prototype relating to nervous system repaired research study residence response retinal rods ribbon synapse second harmonic sensory system size skills software development software systems solid state spatial relationship spinal nerve posterior root synaptic function synaptogenesis time use transmission process two-photon user-friendly voltage voltage clamp voltage gated channel wasting

项目摘要

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.

2P 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，神经元必须有效地沟通与彼此。这种通讯是通过称为突触的特殊结构完成的。绝大多数突触接触是在神经元树突上进行的。树突中发现的突触复合体很复杂由突触前细胞和突触后细胞之间的合作创建的转导机器。树突状膜在突触专业化之外，还有一个高度专业化、动态的结构，其中投入了大量的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。关于树突在健康和疾病中的作用的基本见解正在从我们的研究中浮现出来。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 组是由博士的招募而核心。纳尔逊·斯普鲁斯顿 (Nelson Spruston) 和凯瑟琳·伍利 (Catherine Wooley)，国际公认的领导者在神经元树突的研究中。 2001 年，James Surmeier 博士被聘为生理学系主任密克罗尼西亚联邦部门。在神经调节机制研究方面享有盛誉对神经元树突状功能至关重要，他启动了一项战略计划，以大幅扩展该组 NU 在这一领域工作的神经科学家。该决定基于 1) 该领域的现有优势， 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的紊乱。随着招募十二名在过去三年里，新教师进入这一领域，这个群体已经达到了临界数量。虽然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 NIH 的大力资助，在 2004-05 年获得了大约 1200 万美元，其中 $XM 来自 NINDS。随着许多具有 2P 专业知识的年轻新兵（例如 P. Osten、J. Waters、 G. Shepherd）今年将向 NINDS 提交第一笔赠款。总的来说，这个小组代表了最大、最有经验的生理学家群体之一在世界范围内追求树突和突触生理学（表1A）。大多数是经验丰富的电生理学家，还有几位是树突电记录方面的专家（Spruston、Maccaferri、Martina、Waters、奥斯汀）。其中几位是使用光学方法研究枝晶特性的专家（Hockberger、Spruston、格鲁岑德勒、谢泼德、彭泽斯、沃特斯、奥斯滕）。其他人目前正在开发这种专业知识（Surmeier， Bevan、Mintz、Martina、Singer），该领域的出版物开始出现（例如 Surmeier 的实验室：Day 等人，《自然神经科学》，2006 年 2 月）。大多数研究人员都在同一部门（生理学）他们有机会每天相互交流。大多数人都在眼科和神经科有相邻的实验室。苏梅尔、米勒、拉奥和贝文合而为一大型开放实验室空间。大多数参与教师的邻近性为异花受精创造了独特的机会的想法和合作。因为每个研究人员都提出了关于树突和突触的重要问题，所以一个明确的 NINDS 和 NU 投资收益最大化的障碍是他们获得的机会有限非线性光学技术。在过去三年中，NU 已采取措施纠正这一限制，制定了主要投资在空间、设备和人员方面。该提案旨在以这项投资为基础这项技术可供整个 NU 的研究人员使用。