NeuroNex Innovation Award: Voltage to Light Transducers (VoLT) Collaborative

NeuroNex 创新奖：电压光传感器 (VoLT) 协作

基本信息

批准号：
1707359
负责人：
Francois St-Pierre
金额：
$ 80万
依托单位：
Baylor College of Medicine
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1707359&HistoricalAwards=false
关键词：
NeuroNex Innovation Award Voltage Light

项目摘要

The ability to image brain activity is critical to understand how we learn, think, sense, plan movements, and behave. It can also help understand how neurological disorders impact brain function, paving the way for cures or treatments. A major challenge is that brain activity is rapid (millisecond-timescale) and operates at spatial scales down to less than 1/1000th of a millimeter. There are existing tools to image brain activity, but they have important limitations, such as being too slow to follow fast brain activity, having poor spatial resolution, being unable to record from many brain cells or only allowing imaging at the very surface of the brain. The investigators of this project are developing new sensors for imaging brain activity in animal models, thereby providing the research community with more powerful tools to study the brain in health and disease. The investigators engineer "voltage indicators," which are proteins who emit flashes of light when neurons are active. Previous studies demonstrated the potential for this technology, but developing better versions is laborious and time-intensive. Here, a new methodology for rapidly improving voltage indicators is being developed and disseminated to the broader community of neuroscientists and other biologists. The technology enables users to obtain improved versions on an accelerated timescale. The project also affords multi-disciplinary training opportunities for graduate students.Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits, but is challenging due to the limited performance of existing tools. The investigators address this technical need by developing Genetically Encoded Voltage Indicators (GEVIs), membrane-based fluorescent proteins whose brightness is modulated by transmembrane voltage. This emerging technology promises to fulfill the dream of recording electrical activity from many cells or subcellular locations in vivo and with cell type specificity. While GEVIs have enabled a restricted number of experiments in vivo, further improvement of their performance will be needed for broader use of these probes in vivo. In particular, GEVIs would benefit from increased sensitivity, brightness and photostability. To address the limitations of current indicators, the investigators are developing a microscopy platform that can rapidly screen indicator variants by automatically monitoring the variants' fluorescence responses to voltage changes. The investigators also are constructing several libraries of indicator variants, focusing on residues that are important for sensing the electrical field, or controlling fluorescence excitation or emission. The resulting indicators are characterized comprehensively across all key performance metrics to facilitate deployment in downstream applications. This NeuroNex Innovation Award is part of the BRAIN Initiative and NSF's Understanding the Brain activities.

图像大脑活动的能力对于了解我们学习，思考，感知，计划运动和行为至关重要。它还可以帮助理解神经系统疾病如何影响大脑功能，为治愈或治疗铺平道路。一个主要的挑战是，大脑活动是迅速的（毫秒时刻），并且在空间尺度下运行至毫米小于1/1000毫米。现有的工具可以图像大脑活动，但是它们具有重要的局限性，例如太慢，无法遵循快速的大脑活动，空间分辨率差，无法从许多脑细胞中记录，或者仅允许在大脑表面进行成像。该项目的研究人员正在开发新的传感器，以对动物模型中的大脑活动进行成像，从而为研究社区提供了研究健康和疾病大脑的更强大的工具。研究人员的工程师“电压指示器”是蛋白质，当神经元活跃时会发出光闪光。先前的研究证明了这项技术的潜力，但是开发更好的版本是费力且耗时的。在这里，正在开发和传播一种快速改善电压指标的新方法，并传播到更广泛的神经科学家和其他生物学家社区。该技术使用户能够在加速时间范围内获得改进的版本。该项目还为研究生提供了多学科的培训机会。大脑深处定义的神经元的监控电压动态对于揭示神经元电路的功能至关重要，但是由于现有工具的性能有限，因此具有挑战性。研究人员通过开发遗传编码的电压指标（GEVIS），基于膜的荧光蛋白来解决这种技术需求，其亮度通过跨膜电压调节。这项新兴技术有望实现从许多细胞或细胞类型特异性中从许多细胞或亚细胞位置记录电活动的梦想。尽管Gevis在体内启用了限制数量的实验，但在体内更广泛使用这些探针将需要进一步提高其性能。特别是，Gevis将受益于提高灵敏度，亮度和光稳定性。为了解决当前指标的局限性，研究人员正在开发一个显微镜平台，该平台可以通过自动监视变体对电压变化的荧光响应来快速筛选指标变体。研究人员还正在构建几个指标变体的文库，重点关注对感测电场或控制荧光激发或发射至关重要的残基。所得指标在所有关键性能指标中都具有全面的特征，以促进下游应用程序中的部署。该神经元创新奖是大脑计划的一部分，而NSF理解了大脑活动。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Versatile phenotype-activated cell sorting.

DOI：
10.1126/sciadv.abb7438
发表时间：
2020-10
期刊：
Science advances
影响因子：
13.6
作者：
Lee J;Liu Z;Suzuki PH;Ahrens JF;Lai S;Lu X;Guan S;St-Pierre F
通讯作者：
St-Pierre F

A synthetic circuit for buffering gene dosage variation between individual mammalian cells.

DOI：
10.1038/s41467-021-23889-0
发表时间：
2021-07-05
期刊：
Nature communications
影响因子：
16.6
作者：
Yang J;Lee J;Land MA;Lai S;Igoshin OA;St-Pierre F
通讯作者：
St-Pierre F

Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators

DOI：
10.7554/elife.25690
发表时间：
2017-07-27
期刊：
ELIFE
影响因子：
7.7
作者：
Chamberland, Simon;Yang, Helen H.;St-Pierre, Francois
通讯作者：
St-Pierre, Francois

Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling.

DOI：
10.1016/j.cub.2021.11.055
发表时间：
2022-02-07
期刊：
Current biology : CB
影响因子：
0
作者：
Behrens C;Yadav SC;Korympidou MM;Zhang Y;Haverkamp S;Irsen S;Schaedler A;Lu X;Liu Z;Lause J;St-Pierre F;Franke K;Vlasits A;Dedek K;Smith RG;Euler T;Berens P;Schubert T
通讯作者：
Schubert T

Ancestral circuits for vertebrate color vision emerge at the first retinal synapse.