Multimodal probes for multiscale calcium imaging

用于多尺度钙成像的多模态探针

• 批准号: 10154098
• 负责人: Alan Jasanoff
• 金额: $ 23.18万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10154098
• 关键词: Acids; Analytical Chemistry; BRAIN initiative; Behavior; Behavioral; Brain; Calcium; Calcium Binding; Calcium Signaling; Cell Fractionation; Cells; Charge; Chelating Agents; Chemicals; Complex; Contrast Media; Development; Esters; Ethane; Fluorescence; Functional Magnetic Resonance Imaging; Gadolinium; Goals; Histology; Image; In Vitro; Individual; Ionophores; Ions; Lanthanoid Series Elements; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Mediating; Metals; Methodology; Methods; Modality; Molecular; Morphologic artifacts; Neurons; Optics; Performance; Permeability; Porphyrins; Property; Rattus; Reporter; Research Personnel; Resolution; Role; Signal Transduction; Source; Techniques; Technology; Testing; Texaphyrin; Titrations; Transition Elements; Validation; Variant; Yttrium; base; design; experimental study; fluorescence imaging; fluorophore; hydrophilicity; imaging agent; imaging capabilities; imaging modality; in vivo; innovation; multimodality; neurodevelopment; neuroimaging; non-invasive imaging; novel; novel strategies; optical imaging; optoacoustic tomography; photoacoustic imaging; relating to nervous system; response; sensor; spatiotemporal; tool; validation studies

A major goal of the BRAIN Initiative is to promote the development of neural activity measurement tools that bridge between spatial scales, so that the processing roles of individual neurons and microcircuits can be related to broader regional or brain-wide dynamics. Here we propose to create novel chemical probes of neuronal cal- cium signaling that will enable cross-modal comparison of readouts obtained at multiple scales, using both inva- sive and noninvasive imaging methods. Using these multifunctional probes, investigators will be able to record wide-field neural activity dynamics at varying depths and spatiotemporal resolutions from well-defined molecular sources that permit precise interpretation, without the potential for artifacts associated with parallel application of disparate probe modalities. This will be particularly valuable for validation and use of the probes in noninvasive imaging modalities, for which probe technologies are still relatively rudimentary and untested, and relating wide- field signals to micron-resolution optical results could be especially informative. The new probes we will create are derived from a cell-permeable aromatic chelator called texaphryin (Tex). Complexes of Tex variants with different metal ions function as potent fluorophores, photoacoustic reporters, and T1-weighted contrast agents for magnetic resonance imaging (MRI). We recently discovered that combining paramagnetic Tex complexes with calcium-responsive moieties such as 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) results in strong calcium-dependent contrast changes, thus providing a promising basis for synthesis of sensors suitable for simultaneous or parallel measurement by MRI, optical, and photoacoustic readouts. In this project, we will synthesize and optimize the multimodal sensors, evaluate their optical and magnetic imaging capabilities, and begin in vivo validation studies that directly exploit the unique advantages these novel probes offer. These experiments will establish a first-of-its-kind molecular platform with potentially powerful capability for multimodal analysis of neural activity dynamics across spatial and temporal scales in a variety of species and behavioral contexts.

BRAIN Initiative 的一个主要目标是促进神经活动测量工具的开发， 空间尺度之间的桥梁，以便将单个神经元和微电路的处理作用联系起来 在这里，我们建议创建新的神经钙化学探针。 cium 信号将能够使用 inva- 方法对在多个尺度上获得的读数进行跨模式比较 使用这些多功能探头，研究人员将能够记录。 来自明确分子的不同深度和时空分辨率的广域神经活动动力学 允许精确解释的来源，而不会出现与并行应用程序相关的伪影 这对于非侵入性探头的验证和使用特别有价值。 成像模式，其探针技术仍然相对初级且未经测试，并且涉及广泛 我们将创建的新探针可以提供特别丰富的信息。 衍生自一种称为 texaphryin (Tex) 的细胞渗透性芳香螯合剂，其具有 Tex 变体的复合物。 不同的金属离子充当有效的荧光团、光声产生器和 T1 加权造影剂 我们最近发现结合顺磁 Tex 复合物。 具有钙响应部分，例如 1,2-双（邻氨基苯氧基）乙烷-N,N,N',N'-四乙酸 (BAPTA) 导致强烈的钙依赖性对比度变化，从而为传感器的合成提供了有前景的基础 适用于 MRI、光学和光声读数的同步或并行测量。 我们将合成和优化多模态传感器，评估其光学和磁成像能力， 并开始体内验证研究，直接利用这些新型探针提供的独特优势。 实验将建立一个首个具有潜在强大多模态能力的分子平台 分析各种物种和行为的跨空间和时间尺度的神经活动动态 上下文。