Two-photon optical control of astrocytic function

星形胶质细胞功能的双光子光学控制

基本信息

批准号：
8557604
负责人：
RAFAEL YUSTE
金额：
$ 39.59万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-25 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8557604
关键词：
Affect Algorithms Animals Area Astrocytes Award Biological Assay Brain Buffers Calcium Cells Communities Computational algorithm Detection Disease Functional disorder Future Gap Junctions Gene Activation Gene Expression Genes Genetic Giant Cells Glutamates Goals Housekeeping Image Individual Investigation Life Light Measures Methods Microscopy Mus Nervous system structure Neuroglia Neurons Neurosciences Neurotransmitters Optical Methods Optics Outcome Pattern Play Population Process Psyche structure Recycling Research Research Personnel Resolution Role Sampling Shapes Slice Synapses Synaptic Transmission System Techniques Therapeutic Three-Dimensional Imaging Tissues Weight Work area striata awake computerized tools extracellular in vivo information processing member neural circuit novel operation optogenetics photoactivation public health relevance spatiotemporal tissue fixing tool two-photon

项目摘要

DESCRIPTION (provided by applicant): Astrocytes are not merely passive members of the circuit, but that they may also be directly involved with neuronal computation. Indeed, astrocytes are well suited to a potential widespread role in the circuit: they tile the CNS with near- complet coverage, are connected into an extensive syncytium via gap junctions, and processes from a single astrocyte can contact up to tens of thousands of synapses. In fact, we have recently shown how even the stimulation of single astrocyte can control circuit-wide neuronal synchronizations in the cortex. Tools to study astrocytes are significantly less developed than those available to investigate neuronal function and, consequently, most research on astrocytic information processing has been limited and incomplete. Astrocyte researchers need methods to selectively measure and manipulate the function of astrocytes in vivo. Two-photon excitation, which penetrates living tissue while affording single-cell resolution, combined with compatible optochemical or optogenetic probes, could be an ideal technical platform for future astrocyte research. We propose to develop novel two-photon and computational tools to provide subcellular and circuit-level analysis of astrocytic function in neural circuits in vivo, using a nvel astrocyte-specific Brainbow mouse line. These tools include two- photon optogenetic and caged compounds, methods to image groups of astrocytes in 3D, and computational algorithms to reveal interactions of astrocytes with neurons in the circuit. With this award, we will provide the astroglia community with a wide range of optical and computational tools that can be readily adapted for use in vivo. This work will enable the investigation of the roles of astrocytes in shaping neuronal activity in the cortical microcircuit and beyond, and thus could have a fundamental impact on how we view neuro-glia processing, as well as on solidifying the role of an overlooked circuit constituent-the astrocyte-in cortical synchrony and computation. Finally, this work could introduce a novel potential means to assay or control neuronal function for potential therapeutic purposes: through specific activation of astrocytes.

描述（由申请人提供）：星形胶质细胞不仅是电路的被动成员，而且还可能直接参与神经元计算。实际上，星形胶质细胞非常适合在电路中发挥潜在的广泛作用：它们的中枢神经系统覆盖了几乎完成，通过间隙连接连接到广泛的合成中，并且来自单个星形胶质细胞的过程可以接触多达数万个突触。实际上，我们最近展示了即使刺激单个星形胶质细胞也可以控制皮层中电路范围的神经元同步。研究星形胶质细胞的工具明显少于研究神经元功能的工具，因此，大多数关于星形胶质细胞信息处理的研究都是有限且不完整的。星形胶质细胞研究人员需要选择性测量和操纵体内星形胶质细胞功能的方法。两光子激发在提供单细胞分辨率的同时穿透活组织，再加上兼容的验光或光遗传学探针，可能是未来星形胶质细胞研究的理想技术平台。我们建议使用NVEL Astrocyte特异性的Brainbow小鼠系列开发新型的两光子和计算工具，以提供体内神经回路中星形胶质细胞功能的亚细胞和电路级分析。这些工具包括两种光子光遗传学和笼子化合物，图像图像中的星形胶质细胞组的方法以及计算算法，以揭示星形胶质细胞与电路中神经元的相互作用。有了这个奖项，我们将提供具有各种光学和计算工具的星形胶质体社区，可以容易适用于体内。这项工作将使星形胶质细胞在塑造皮质微电路及其他地区的神经元活性中的作用进行研究，从而对我们如何看待神经性glia处理以及巩固被忽视的被忽视的反应组成型体形磁管中的皮质同步和计算的作用，从而产生根本性的影响。最后，这项工作可以引入一种新的潜在手段，以分析或控制潜在治疗目的的神经元功能：通过星形胶质细胞的特定激活。