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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：
7616845
负责人：
David Wokosin
金额：
$ 7.31万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7616845
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.

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之间。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在活组织中动态地可视化这些微观区域。 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。