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

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).

抽象的描述特定大脑功能背后的特定神经身份和连接性仍然存在一个多世纪以来，神经解剖学一直在神经科学的核心目标中发挥着关键作用。参考神经元的突触接触、树突形态和轴突投影来确定其连接性。基因探针、光学成像方式和计算机技术的进步使得监测成为可能并以前所未有的精度和规模操纵活体动物的神经活动。 “组学”研究的前沿开始区分异质的分子多样性同一大脑区域中的群体神经元进一步鉴定独特的分子标记。能够创建新颖的转基因模型来询问神经元的精确子集。将这些革命性技术应用于研究系统和行为取得了巨大成功神经科学，目前缺乏统一的实验范式来直接联系活动、连接以及单细胞/单功能回路中完全相同的神经元的分子信息这样做的能力将消除当前尝试关联不同的歧义。从不同动物身上采集的“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区分特定神经网络的效率和准确性与同一大脑区域的不同回路功能相关的群体。在这里，我们展示了 coMAAP 的可行性，这是一种多模式实验范式，允许同一神经元的活动、解剖结构和分子身份的相关光学映射重要的是，coMAAP 可以使用标准仪器来实施。专门的成像方式它可以实现前所未有的分辨率和规模我们的目标。建议优化和验证 coMAAP 实验范例，并利用 coMAAP 描绘了小鼠腹侧被盖中被唤醒激活的异质神经元群区域（VTA）。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology.

亚细胞级碳纤维皮质内电极和周围神经元的外植后分析可以对记录的电生理学进行建模。

DOI：
发表时间：
2023-03-17
期刊：
影响因子：
0
作者：
Letner, Joseph G;Patel, Paras R;Hsieh, Jung;Smith Flores, Israel M;Della Valle, Elena;Walker, Logan A;Weiland, James D;Chestek, Cynthia A;Cai, Dawen
通讯作者：
Cai, Dawen