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RII Track-2 FEC: The Creation of Next-Generation Tools for Neuroscience - Noninvasive Radioluminescence Approaches to Optogenetics

RII Track-2 FEC：下一代神经科学工具的创建 - 光遗传学的无创放射发光方法

基本信息

批准号：
1632881
负责人：
Stephen Foulger
金额：
$ 600万
依托单位：
Clemson University
依托单位国家：
美国
项目类别：
Cooperative Agreement
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1632881&HistoricalAwards=false
关键词：
RII Track FEC Creation Next

项目摘要

Non-Technical DescriptionThis Research Infrastructure Improvement Track-2 Focused EPSCoR Collaboration (RII Track-2 FEC) proposal is a collaboration between four institutions in South Carolina, Alabama, and New Mexico, namely Clemson University, the University of Alabama Birmingham, the University of New Mexico, and the University of South Carolina. The aim of the project is to extend the uses of the experimental method of optogenetics, which, since its introduction in 2005, has had a transformative impact on neurobiology. This method allows experimenters to activate individual neurons or groups of neurons, with high levels of spatial and temporal control, by flashing light on them. One of the main limitations of standard optogenetics is the inability of visible light to penetrate deep within living tissues. In this project, a system will be developed to allow the use of low-dosage X-rays, rather than visible light, as the activating signal. The project includes multiple opportunities to involve students, especially members of under-represented minority groups. Agreements are in place to host students from Winthrop University and Northern New Mexico College, which serve highly diverse student populations, in existing summer research programs at the research-intensive universities. The project also includes plans for mentoring junior faculty, especially in proposal development.Technical DescriptionThis multi-disciplinary project involves step-wise development of novel experimental methods. First, radioluminescent nanoparticles (RLPs) will be produced that emit light when exposed to X-rays. The RLPs will be chemically modified to allow specific covalent attachment to a genetically engineered membrane-bound opsin protein expressed in neurons, ensuring close proximity of the two components for efficient transfer of the light stimulus. The system will be tested (for efficacy and the absence of undesired side effects) in cultured cells, then brain slice preparations, and finally in intact animals (rats and mice). RLPs will be introduced into animals by injection into the cerebrospinal fluid, through which the particles may diffuse into the brain. The effects of X-ray exposure on the behavior of immobilized and freely moving animals will then be tested to verify successful activation of neural cells in the motor and auditory cortexes.

非技术说明这项以研究基础设施改进 Track-2 为重点的 EPSCoR 合作 (RII Track-2 FEC) 提案是南卡罗来纳州、阿拉巴马州和新墨西哥州的四所机构之间的合作，即克莱姆森大学、阿拉巴马大学伯明翰分校、新墨西哥大学和南卡罗来纳大学。该项目的目的是扩展光遗传学实验方法的用途，该方法自 2005 年推出以来，对神经生物学产生了变革性的影响。这种方法允许实验者通过闪光来激活单个神经元或神经元组，并进行高水平的空间和时间控制。标准光遗传学的主要局限性之一是可见光无法深入活体组织。在该项目中，将开发一种系统，允许使用低剂量 X 射线而不是可见光作为激活信号。该项目包括多种让学生参与的机会，特别是代表性不足的少数群体的成员。已达成协议，接待来自温思罗普大学和北新墨西哥学院的学生，参加研究密集型大学现有的夏季研究项目，这两个学院为高度多样化的学生群体提供服务。该项目还包括指导初级教师的计划，特别是在提案制定方面。技术描述这个多学科项目涉及新颖实验方法的逐步开发。首先，将产生放射发光纳米颗粒（RLP），当暴露于 X 射线时会发光。 RLP 将经过化学修饰，以允许与神经元中表达的基因工程膜结合视蛋白特异性共价连接，确保两个组件紧密接近，从而有效传输光刺激。该系统将在培养细胞中进行测试（有效性和是否存在不良副作用），然后在脑切片制剂中进行测试，最后在完整的动物（大鼠和小鼠）中进行测试。 RLP 将通过注射到脑脊液中引入动物体内，颗粒可以通过脑脊液扩散到大脑中。然后将测试 X 射线照射对固定和自由移动动物行为的影响，以验证运动和听觉皮层神经细胞的成功激活。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

X-ray Radioluminescent Crystalline Colloidal Arrays Composed of Terpolymer Nanoparticles

由三元聚合物纳米颗粒组成的 X 射线辐射发光晶体胶体阵列

DOI：
10.1364/noma.2021.nof3b.6
发表时间：
2021
期刊：
OSA Advanced Photonics Congress 2021
影响因子：
0
作者：
Jones, Haley W.;Bandera, Yuriy;Foulger, Stephen H.
通讯作者：
Foulger, Stephen H.

Diverse Mechanisms Lead to Common Dysfunction of Striatal Cholinergic Interneurons in Distinct Genetic Mouse Models of Dystonia

DOI：
10.1523/jneurosci.0407-19.2019
发表时间：
2019-09-04
期刊：
JOURNAL OF NEUROSCIENCE
影响因子：
5.3
作者：
Jaunarajs, Karen L. Eskow;Scarduzio, Mariangela;Standaert, David G.
通讯作者：
Standaert, David G.

Synthesis and characterization of modular polyphosphonate homopolymers and copolymers

模块化聚膦酸酯均聚物和共聚物的合成和表征

DOI：
10.1002/pol.20200066
发表时间：
2020
期刊：
Journal of Polymer Science
影响因子：
3.4
作者：
Totsch, Timothy R.;Stanford, Victoria L.;Klep, Oleksander;Burdette, Mary K.;Grant, Benjamin;Foulger, Stephen H.;Gray, Gary M.
通讯作者：
Gray, Gary M.

Exploiting multiple percolation in two-terminal memristor to achieve a multitude of resistive states