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Synaptomes of Mouse and Man

小鼠和人的突触

基本信息

批准号：
9323837
负责人：
Randal Burns
金额：
$ 168.09万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9323837
关键词：
Acetylcholine Animal Experimentation Animals Array tomography Brain Brain Diseases Brain region Chemical Synapse Chemicals Clinical Complex Computers Computing Methodologies Data Data Analytics Development Diagnosis Dimensions Disease Dopamine Elements Experimental Models Fiber Foundations Future G-Protein-Coupled Receptors Genes Human Image Individual Letters Maps Measurement Measures Mediating Mental Health Mental disorders Methods Modeling Molecular Molecular Analysis Molecular Models Mus Neuraxis Neurodegenerative Disorders Neurodevelopmental Disorder Neuromodulator Neurons Neurosciences Neurotransmitters Norepinephrine Physiological Plant Roots Plasticizers Population Population Analysis Population Heterogeneity Protein Isoforms Proteins RNA Splicing Reagent Resolution Resources Science Scientist Serotonin Signal Transduction Signaling Protein Specimen Speed Structure Synapses Synaptic Transmission Technology Temporal Lobe Tissues Variant Work base brain abnormalities brain research differential expression flexibility frontal lobe imaging modality innovation insight interest man molecular assembly/self assembly molecular modeling multidisciplinary neural circuit neuronal circuitry neuroregulation novel postsynaptic presynaptic prevent public health relevance receptor tool

项目摘要

DESCRIPTION (provided by applicant): The synapse is the principle active signaling component of the brain's neuronal circuitry. Synapses are highly complex, plastic, strongly modulated and deeply diverse entities, and their molecular complexity and diversity are fundamental to all synaptic circuit development and function. Moreover, many or most neurodevelopmental, psychiatric, and neurodegenerative disorders are rooted in abnormalities of the brain's vast and highly heterogeneous synapse populations. Unfortunately, such disorders are poorly understood and difficult to diagnose, prevent, and treat because we lack adequate tools to measure the brain's vast and highly diverse synapse populations, and because most of the limited tools in use today can be applied only to experimental animals such as mice. An interdisciplinary consortium comprising neurobiologists, biophysicists, clinicians, mathematicians and computer scientists here proposes development of a very ambitious "synaptomic" analysis pipeline that will transform the science of synaptic network function and disorders in both experimental animal and human brains. This novel high-throughput pipeline, based on powerful new array tomography methods, will enable measurement, analysis, and modeling of heterogeneous synapse and neuromodulatory fiber populations with unprecedented precision. The synaptomic pipeline will be demonstrated initially by developing "synaptomes" to model the heterogeneous synapse populations of mouse and human frontal and temporal lobes. Pipeline resources and data will then be shared via an Open Synaptome Project that will facilitate the development of synaptomes describing synapse populations of additional brain regions and species. These efforts are expected to provide a new foundation for understanding the basic mechanisms of mammalian brain function, and to offer new quantitative perspectives on both similarities and differences between mouse and human brain that will be critical to leveraging animal research opportunities for the improvement of human mental health. Because abnormalities of synapses and their neuromodulation are prime suspects in numerous human mental health disorders, the development and sharing of synaptomic pipeline resources and data proposed here are likely to catalyze rapid progress in clinical neuroscience.

描述（由申请人提供）：突触是大脑神经元回路的主要活性信号成分。突触是高度复杂、可塑性强、调节性强且高度多样化的实体，其分子复杂性和多样性是所有突触回路发育和功能的基础。此外，许多或大多数神经发育、精神病和神经退行性疾病的根源在于大脑巨大且高度异质的突触群的异常。不幸的是，人们对这种疾病知之甚少，难以诊断、预防和治疗，因为我们缺乏足够的工具来测量大脑中巨大而高度多样化的突触群，而且今天使用的大多数有限的工具只能应用于实验动物，如小鼠。一个由神经生物学家、生物药理学家、临床医生、数学家和计算机科学家组成的跨学科联盟在这里提出了一个非常雄心勃勃的“突触”分析管道的发展，这将改变实验动物和人类大脑中突触网络功能和疾病的科学。这种新型的高通量流水线，基于强大的新阵列断层扫描方法，将使测量，分析和建模的异质性突触和神经调节纤维群体具有前所未有的精度。突触组学管道将通过开发“突触组”来模拟小鼠和人类额叶和颞叶的异质突触群体来初步展示。管道资源和数据将通过开放突触组项目共享，该项目将促进描述其他大脑区域和物种的突触群体的突触组的开发。这些努力有望为理解哺乳动物大脑功能的基本机制提供新的基础，并为小鼠和人类大脑之间的相似性和差异提供新的定量视角，这对于利用动物研究机会改善人类心理健康至关重要。由于突触异常及其神经调节是许多人类精神健康疾病的主要嫌疑人，因此这里提出的突触管道资源和数据的开发和共享可能会催化临床神经科学的快速进步。