A multimodal platform to bridge the experimental gap between behavioral, neuronal, and molecular studies

弥合行为、神经元和分子研究之间实验差距的多模式平台

基本信息

批准号：
9794177
负责人：
Dawen Cai
金额：
$ 225.11万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9794177
关键词：
Anatomy Animals Antigens Arousal Axon Behavior Behavioral Brain Brain region Calcium Cells Computers Custom Data Endoscopes Female Genetic Goals Home environment Image In Vitro Knowledge Lateral Light Link Maps Mental disorders Microscope Molecular Monitor Morphology Mus Neuroanatomy Neurons Neurosciences Optics Performance Play Population Process Proteins Protocols documentation Resolution Role Sampling Slice Speed Stains Synapses System Technology Thick Tissue Expansion Tissue Preservation Tissues Transgenic Model Ventral Tegmental Area base calcium indicator connectome high resolution imaging imaging modality imaging system improved in vivo instrument male microscopic imaging millimeter molecular marker multimodality multiplex detection nanometer neural network neuronal circuitry new technology novel optical imaging preservation protein biomarkers prototype success transcriptome

Anatomy Animals Antigens Arousal Axon Behavior Behavioral Brain Brain region Calcium Cells Computers Custom Data Endoscopes Female Genetic Goals Home environment Image In Vitro Knowledge Lateral Light Link Maps Mental disorders Microscope Molecular Monitor Morphology Mus Neuroanatomy Neurons Neurosciences Optics Performance Play Population Process Proteins Protocols documentation Resolution Role Sampling Slice Speed Stains Synapses System Technology Thick Tissue Expansion Tissue Preservation Tissues Transgenic Model Ventral Tegmental Area base calcium indicator connectome high resolution imaging imaging modality imaging system improved in vivo instrument male microscopic imaging millimeter molecular marker multimodality multiplex detection nanometer neural network neuronal circuitry new technology novel optical imaging preservation protein biomarkers prototype success transcriptome

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项目摘要

ABSTRACT Depicting the specific neuronal identity and connectivity underlying particular brain function remains a central goal for neuroscience. For over a century, neuroanatomy has continued to play critical roles in referencing a neuron's synaptic contact, dendritic morphology and axonal projection to its connectivity. The advances of genetic probes, optical imaging modalities and computer technologies permit monitoring and manipulating neuronal activity in living animals with unprecedented precision and scale. In addition, the forefront of “-omics” study begins to discriminate the molecular diversity of the heterogenous population neurons in the same brain region. The identification of unique molecular markers further enables creating novel transgenic models to interrogate precise subsets of neurons. Despite the tremendous success in applying these revolutionary technologies in studying systems and behavior neuroscience, there currently lacks a unified experimental paradigm to directly link activity, connection and molecular information of the exact same neurons in a functional circuit at the single cell/single synapse resolution. The ability to do so will remove the ambiguity in current attempts to correlate different attributes of the “same” neuronal populations sampled from different animals. More importantly, the ability to do so will tremendously improve our efficiency and accuracy in differentiating specific neuronal populations that correlate with distinct circuit functions in the same brain region. Here, we demonstrate the feasibility of coMAAP, a multimodal experimental paradigm that allows correlative optical mapping of activity, anatomy and molecular-identity of the same neurons in the same animal. Importantly, coMAAP can be implemented using standard instruments. While combining with specialized imaging modalities it can achieve unprecedented resolution and scale. The goals of our proposal are to optimize and validate the coMAAP experimental paradigm, and to utilize coMAAP to depict the heterogenous neuronal populations that are arousal activated in the mouse ventral tegmental area (VTA).

抽象的描述特定特定大脑功能的特定神经元身份和连通性仍然存在神经科学的中心目标。一个多世纪以来，神经解剖学一直在将神经元的突触接触，树突形态和轴突投射引用到其连通性。遗传问题，光学成像方式和计算机技术的进步允许监视并在具有前所未有的精度和尺度的活动物中操纵神经元活性。此外， “ - 组”研究的最前沿开始区分异质的分子多样性同一大脑区域的人群神经元。进一步识别独特的分子标记使创建新型的转基因模型来询问神经元的精确子集。尽管有将这些革命性技术应用于研究系统和行为方面的巨大成功神经科学，目前缺乏统一的实验范式直接连接活动，连接在单个单元/单个单元的功能电路中完全相同的神经元的分子信息突触分辨率。这样做的能力将消除当前尝试与不同的尝试的歧义从不同动物中取样的“相同”神经群体的属性。更重要的是，能力这样做将极大地提高我们在区分特定神经元方面的效率和准确性与同一大脑区域中不同电路功能相关的种群。在这里，我们演示了Comaap的可行性，Comaap是一种多模式实验范式，允许相同神经元的活性，解剖学和分子认同的相关光学映射动物。重要的是，可以使用标准仪器实施COMAAP。在与之结合的同时专门的成像方式可以实现前所未有的分辨率和规模。我们的目标建议将优化和验证Comaap实验范式，并利用Comaap 描述在小鼠腹侧段中激活的异质神经元种群区域（VTA）。