Ultrashort Pulsed Laser Light for the Manipulation of Neurons and Vasculature

用于操纵神经元和脉管系统的超短脉冲激光

• 批准号: 0455027
• 负责人: David Kleinfeld
• 金额: $ 69.22万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0455027&HistoricalAwards=false
• 关键词: Ultrashort; Pulsed; Laser; Light; Manipulation

The advent of ultrashort laser light pulses as a laboratory tool has provided the opportunity to probe and manipulate structure and function in biological systems. This award supports development of an instrument that will use nonlinear absorption to create micrometer-sized ablations in nervous tissue, with minimal collateral damage. The instrument can be integrated with existing nonlinear imaging devices, principally the multi-photon microscope. Prior work has shown that ultrashort laser pulses can be used for an all-optical approach to histology in which anatomical structure with micrometer resolution is obtained without the use of mechanical sectioning devices. Pilot data has also demonstrated that such pulses can block flow in specific, targeted blood vessels, thus enabling studies of the biofluid mechanics of the vessels. The proposed instrument development program will design and realize ultrashort pulsed laser technology capable of a mixture of optical ablation and nonlinear optical imaging. The effort will result in a near turn-key system that uses commercially available laser oscillators and regenerative amplifiers, together with a mixture of commercial and custom opto-mechanical and electronic components and software. The expected applications include the automatic anatomical mapping of neuronal and non-neuronal nuclei, vasculature, and subcellular structures within the rodent brain, and the optical induction of axonomy in which axons in the leech ganglion are cut to study circuit dynamics in the swim command network. Additional potential applications include submicrometer surgery to ablate organelles, and transient disruption of the blood-brain barrier. The design and realization of the instrument will expose students to use of state-of the art optical instrumentation for the pursuit of biological questions. The proposed work will specifically train two postdoctoral researchers in instrumentation and experimentation at the optics/biology interface.

超短激光脉冲作为一种实验室工具的出现，为探测和操纵生物系统的结构和功能提供了机会。该奖项支持一种仪器的开发，该仪器将使用非线性吸收在神经组织中产生微米大小的消融，附带损害最小。该仪器可以与现有的非线性成像设备集成，主要是多光子显微镜。先前的工作表明，超短激光脉冲可以用于组织学的全光学方法，其中不使用机械切片装置即可获得微米分辨率的解剖结构。试点数据还表明，这种脉冲可以阻断特定的、有针对性的血管中的血流，从而使研究血管的生物流体力学成为可能。提出的仪器开发计划将设计和实现能够混合光学烧蚀和非线性光学成像的超短脉冲激光技术。这项工作将产生一个近乎交钥匙的系统，该系统使用商用激光振荡器和再生放大器，以及商用和定制光机械和电子元件和软件的混合物。预期的应用包括啮齿动物大脑内神经元和非神经元核、脉管系统和亚细胞结构的自动解剖图谱，以及水蛭神经节轴突的光学诱导解剖学，其中切割水蛭神经节中的轴突以研究游泳命令网络中的电路动力学。其他潜在的应用包括亚微米手术以消融细胞器，以及短暂破坏血脑屏障。该仪器的设计和实现将使学生接触到使用最先进的光学仪器来追求生物学问题。这项工作将专门培养两名光学/生物学接口仪器和实验方面的博士后研究人员。