A turn-key optogenetics and electrophysiology measurement system

摘要 据估计，与睡眠相关的睡眠问题，如高级睡眠阶段障碍（ASPD）， 至少1%的中年人患病，患病率随着年龄的增长而增加。虽然有害的影响， 随着年龄的增长，睡眠中断得到了很好的表征，对分子和生理的详细了解， 这些睡眠变化背后的机制非常缺乏。光遗传学结合了 遗传和光学方法直接控制中枢神经系统特定细胞中的神经元事件 系统最近的研究已经证实，控制清醒和慢波睡眠， 可能使用光遗传学方法。这些方法可以用来提供前所未有的 了解衰老过程中的皮质活动。光遗传学领域正在成熟， 商业来源的光遗传学组件;然而，该技术需要多学科的技能 包括化学、光学、生理学、电子学、机械学、软件和系统分析。到 迄今为止，任何单一的实验都需要一个由各个组成部分设计的系统。许多实验室 也有他们希望整合到完整的光遗传学系统中的现有设备。这可能 包括激光器、照相机和潜在行为硬件和软件平台。在这些情况下 数字定时协议（TTL）通常用于保持同步，但也有微妙之处（设备 延迟等）这种方法经常被忽视。本项目的目标是将联合收割机 将光遗传学和电生理学记录整合到用于小鼠的单一交钥匙模块化系统中。的 系统将能够向一个或多个特定脑递送多个可选择波长的光 在啮齿动物的整个生命周期中，同时记录啮齿动物的电信号。 电生理、机械和视觉输入之间的所有同步，以及光学和 刺激输出将通过主定时、数字输入/输出平台以及 复杂的软件定时技术。光遗传学光源和耦合光纤将是 在标准化的探针平台上实现，该探针平台可以使用 立体定位技术。一旦完成，该系统将通过以下方式大大提高科学知识， 为来自多个领域的研究人员提供一站式解决方案， 控制与传统的老化和脑电图为基础的研究。

ABSTRACT Age-related sleep problems such as advanced sleep phase disorder (ASPD) are estimated to affect at least 1% of middle-aged adults and increase in prevalence with age. While the detrimental effects of sleep disruption with aging are well characterized, detailed insights into the molecular and physiological mechanisms underlying these sleep changes are greatly lacking. Optogenetics harnesses a combination of genetic and optical methods to directly control neuronal events in specific cells of the central nervous system. Recent studies have confirmed that control of both wakefulness and slow-wave-sleep are possible using optogenetic methods. These methods can be used to provide an unprecedented understanding of cortical activity in aging. The optogenetics field is maturing and there are numerous commercial sources for optogenetic components; however, the technique requires a multidisciplinary skill set including chemistry, optics, physiology, electronics, mechanics, software, and systems analysis. To date, any single experiment requires a system designed from individual, component parts. Many labs also have existing equipment that they desire to incorporate into a full optogenetics system. This may include lasers, cameras and potentially behavioral hardware and software platforms. In these situations a digital timing protocol (TTL) is often used to maintain synchronization, but there are subtleties (device latency, etc.) to this approach that are often overlooked. The goal of this project is to combine optogenetics and electrophysiological recording into a single turn-key, modular system for mice. The system will be capable of delivering multiple, selectable wavelengths of light to one or more specific brain regions while simultaneously recording electrical signals in rodents throughout the lifespan of the animal. All synchronization between the electrophysiological, mechanical and visual inputs, and optical and stimulus outputs will be precisely controlled via a master timing, digital input/output platform as well as sophisticated software timing techniques. The optogenetics light source and coupling fiber will be implemented on a standardized probe platform that can be easily, and accurately, implanted using stereotaxic techniques. When completed, this system will significantly improve scientific knowledge by providing a turn-key solution for researchers from multiple fields to seamlessly integrate optogenetic control alongside traditional aging and EEG-based studies.