Development of photoconductive stimulation technology for long-term interfacing with living neurons.

开发用于与活神经元长期连接的光电导刺激技术。

• 批准号: RGPIN-2015-04763
• 负责人: Colicos, Michael
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=679652
• 关键词: Development; photoconductive; stimulation; technology; long

Traditionally, the study of cognitive brain function has been approached through the use of either human subjects or animal models. However, technological advances from the last few decades now allow us to use in vitro neuronal systems to investigate in high resolution the underlying mechanisms responsible for higher level brain functions. Understanding and developing technology to investigate neuronal activity patterns has many applications: from directly facilitating our understanding of complex dynamical systems through to the creation of drug screening devices and modeling of neuropathological conditions. Essential to this research has been the development of devices and systems that allow one to both stimulate and record from living neuronal networks. One such technology, photoconductive stimulation, was invented by my colleagues and I in the lab of Yukiko Goda at UCSD. Based on the principle that the conductivity of silicon will change when illuminated by visible light, neurons are first grown on the surface of specifically manufactured silicon wafers. Then, by optically targeting them with light, they can be individually triggered to fire at a user-defined frequency or in a specific non-random pattern. Combined with calcium- or voltage-sensitive dye imaging of the neuronal network's electrical activity, simultaneous two-way communication with hundreds of neurons has become a reality. This proposal seeks to extend the photoconductive stimulation technology in the following ways, for the following specific goals:******1) Development of a long-term neuronal-silicon interface chamber and stimulation methodology for extended or even permanent interfacing with living neuronal cultures.***2) Development of the in situ optical activity recording devices and protocols, to facilitate extended high resolution recording and analysis of neuronal activity.******Central Hypothesis: Through the use of an optically-based neuronal/silicon interface, we have established a non-invasive methodology to gain read/write capability with living neuronal networks. By developing a long-term controlled environment that maintains this functionality, we can pursue critical questions as to the effect of environmental and genetic manipulation of brain circuits, as well as obtain high spatial- and temporal-resolution data necessary to accurately analyze the complex system dynamics of living neuronal networks.******We believe the development of a viable long-term neuronal interface platform will not only bring immediate gains in our understanding of brain function and complex dynamical systems, but will also have numerous applications for integrating with other research and commercial goals.**

传统上，认知脑功能的研究一直通过使用人类受试者或动物模型来进行。然而，过去几十年的技术进步现在使我们能够使用体外神经元系统来高分辨率地研究负责更高水平大脑功能的潜在机制。理解和开发研究神经元活动模式的技术有许多应用：从直接促进我们对复杂动力系统的理解到创建药物筛选设备和神经病理学条件建模。这项研究的关键是开发设备和系统，使人们能够刺激和记录活的神经元网络。其中一项技术，光电导刺激，是由我和我的同事在加州大学圣地亚哥分校的Yukiko Goda实验室发明的。基于硅的导电性在可见光照射下会发生变化的原理，神经元首先在专门制造的硅片表面生长。然后，通过用光来光学瞄准它们，它们可以被单独触发，以用户定义的频率或特定的非随机模式发射。结合神经元网络电活动的钙或电压敏感染料成像，与数百个神经元的同时双向通信已成为现实。该提案寻求以以下方式扩展光电导刺激技术，以实现以下具体目标：**1）开发长期神经元-硅界面室和刺激方法，用于与活神经元培养物的扩展或甚至永久性界面连接。2)开发原位光学活动记录设备和协议，以促进神经元活动的扩展高分辨率记录和分析。**中心假设：通过使用基于光学的神经元/硅接口，我们已经建立了一种非侵入性的方法来获得与活神经元网络的读/写能力。通过开发一个长期受控的环境来保持这种功能，我们可以追求关于环境和遗传操纵脑回路的影响的关键问题，以及获得准确分析活神经元网络的复杂系统动力学所需的高空间和时间分辨率数据。我们相信，一个可行的长期神经元接口平台的开发不仅会为我们对大脑功能和复杂动力系统的理解带来直接的收益，而且还将有许多应用程序与其他研究和商业目标相结合。