Large-scale calcium and voltage imaging to illuminate neural mechanisms of visual experience

项目总结： 大多数生活经验依赖于神经活动来传递关于世界的感觉信息。 神经损伤和中风是昏迷和空间忽视等疾病的主要原因，这些疾病严重 损害视觉体验，而且没有可行的治疗方案。同样，挽救生命的医疗治疗 依赖于全身麻醉的能力，使患者暂时脱离感官世界。当前 麻醉剂通过抑制整个大脑，包括脑干，实现这一点，这是一个重大的健康风险。连 因此，由于未知的原因，全身麻醉有时无法防止手术中的经验，结果 在严重创伤中的病人。这些问题持续存在，造成了负面的健康后果，部分原因是 尽管对感觉编码的机制进行了大量的研究，特别是在视觉方面，但它仍然不清楚 神经活动如何将感觉信息转化为有意识的经验。有很多种理论，每一种 暗示了不同的机制。视觉体验可能来自高阶神经的活动 或者依赖于内置于网络结构中的隐藏的、复杂的交互。经验可能涉及到 本地、重复的网络交互、远程计算或包含和统一网络的全球事件 活动。不幸的是，支持任何这些理论的具体证据都是有限的。现有技术缺乏 要么是识别单个神经元和亚型微观编码特性的特异性，要么是 必要的范围，以同时检测大规模视觉网络中的活动。中国的新兴技术 施尼泽实验室克服了这些技术限制。先进的显微镜和免费光学设备 现在，技术使得同时记录整个视觉网络中的数千个神经元成为可能， 钙离子成像显示与神经放电有关的活动，电压成像显示亚阈值波 与神经通讯相关的动力学。在这个项目中，我们将1。)制定一项旨在隔离的任务 在老鼠模型中的视觉体验，以优化神经记录技术的好处；2)使用最新的- ART光学仪器，用于解析数千个特定类型神经元的动力学 所有可视皮质区域，描述区分可见和不可见感知的活动模式；3)使用 通过抑制枕区来测试感知机制的化学发生操作，枕区是皮质下的一个区域，可以 调节视觉网络。这项工作的结果，作为初步数据支持，将揭示详细的证据 与有意识的视觉感知相关的神经机制，可以区分 当前的理论。这将推动该领域达成数据驱动的共识，并阐明将 在治疗失调症方面发挥作用。

Project Summary: The majority of lived experience depends on neural activity conveying sensory information about the world. Neural trauma and stroke are leading causes of disorders such as coma and spatial neglect, which severely damage visual experience, and there are no viable treatment options. Similarly, life saving medical treatments depend on the ability for general anesthesia to temporarily disconnect patients from the sensory world. Current anesthetics do so by inhibiting the entire brain, including the brainstem, which is a significant health risk. Even so, for unknown reasons, general anesthesia sometimes fails to prevent experiences during surgery, resulting in severe trauma for patients. These problems persist, creating negative health outcomes, in part because despite substantial research into the mechanisms of sensory encoding, particularly in vision, it remains unclear how neural activity transforms sensory information into conscious experience. There are many theories, each suggesting different mechanisms. Visual experience may emerge from the activity of higher-order neural ensembles, or depend on hidden, complex interactions built into network structures. Experience may involve local, recurrent network interactions, long-range computations, or global events that subsume and unify network activity. Unfortunately, concrete evidence supporting any of these theories is limited. Existing technologies lack either the specificity to identify the microscopic encoding properties of individual neurons and subtypes, or the necessary scope to detect activity simultaneously across sizable visual networks. New emerging technology in the Schnitzer lab overcomes these technical limitations. Advanced microscopes and complimentary optical techniques now make it possible to simultaneously record thousands of neurons across the entire visual network, with Ca2+ imaging revealing activity related to neural firing, and voltage imaging revealing subthreshold wave dynamics associated with neural communication. In this project, we will 1.) develop a task designed to isolate visual experience in mouse models to optimize the benefits of neural recording techniques; 2.) use state-of-the- art optical instrumentation to resolve the dynamics of thousands of individual neurons of specific types across all visual cortical areas, characterizing activity patterns that differentiate seen from unseen percepts; 3) use chemogenetic manipulations to test mechanisms of perception by inhibiting the pulvinar, a subcortical area that modulates visual networks. The results of this work, as preliminary data supports, will reveal detailed evidence of neural mechanisms associated with conscious visual perception that can differentiate predictions made by current theories. This will drive the field towards a data-driven consensus and illuminate mechanisms that will be instrumental in treating disorders.