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

大规模钙和电压成像阐明视觉体验的神经机制

• 批准号: 10753172
• 负责人: Michelle Jordan Redinbaugh
• 金额: $ 7.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-10 至 2026-09-09
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753172
• 关键词: Address; Agreement; Anesthetics; Animal Behavior; Animal Model; Appearance; Area; Behavior Control; Behavioral; Behavioral Assay; Biological Assay; Brain; Brain Stem; Calcium; Cells; Cerebral hemisphere; Clozapine; Coma; Communication; Complex; Conscious; Consciousness Disorders; Consensus; Data; Decision Making; Detection; Disease; Emerging Technologies; Event; Feedback; General Anesthesia; Genetic Techniques; Goals; Hallucinations; Health; Image; Imaging Techniques; Individual; Injections; Laboratory mice; Life; Link; Machine Learning; Macular degeneration; Medical; Microscope; Microscopic; Modality; Mus; Nature; Neurons; Operative Surgical Procedures; Optical Illusions; Optics; Outcome; Oxides; Parietal Lobe; Patients; Pattern; Perception; Photons; Play; Process; Property; Psychometrics; Pulvinar structure; Recurrence; Reporting; Research; Resolution; Retina; Risk; Rodent; Role; Sensory; Signal Transduction; Specificity; Stimulus; Stroke; Structure; Study models; Syndrome; System; Techniques; Technology; Testing; Thalamic Nuclei; Thalamic structure; Time; Training; Transgenic Mice; Trauma; Trauma patient; Vision; Visual; Visual Cortex; Visual Perception; Work; area striata; cell type; design; designer receptors exclusively activated by designer drugs; experience; extrastriate visual cortex; genetic manipulation; hippocampal pyramidal neuron; instrument; instrumentation; mouse model; neural; neuroimaging; neuromechanism; new technology; prevent; sensory mechanism; spatial neglect; synthetic drug; theories; visual stimulus; voltage

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.

项目概要： 大多数生活经验取决于传递有关世界的感官信息的神经活动。 神经创伤和中风是昏迷和空间忽视等疾病的主要原因，这些疾病严重影响 损害视觉体验，并且没有可行的治疗方案。同样，挽救生命的医疗 取决于全身麻醉暂时断开患者与感官世界的能力。当前的 麻醉剂通过抑制包括脑干在内的整个大脑来实现这一点，这是一个重大的健康风险。甚至 因此，由于未知的原因，全身麻醉有时无法避免手术期间的经历，从而导致 在对患者造成严重创伤时。这些问题持续存在，造成负面健康结果，部分原因是 尽管对感觉编码机制（特别是视觉）进行了大量研究，但仍不清楚 神经活动如何将感官信息转化为意识体验。理论有很多种，每种都有 提出不同的机制。视觉体验可能源自高阶神经元的活动 集成，或依赖于网络结构中内置的隐藏的、复杂的交互。经验可能涉及 本地、循环网络交互、远程计算或包含和统一网络的全局事件 活动。不幸的是，支持这些理论的具体证据都很有限。现有技术缺乏 识别单个神经元和亚型的微观编码特性的特异性，或者 跨相当大的视觉网络同时检测活动的必要范围。新兴技术在 施尼策实验室克服了这些技术限制。先进的显微镜和免费光学 现在的技术可以同时记录整个视觉网络中的数千个神经元， Ca2+ 成像揭示与神经放电相关的活动，电压成像揭示阈下波 与神经通讯相关的动力学。在这个项目中，我们将 1.) 开发一个旨在隔离的任务 小鼠模型的视觉体验，以优化神经记录技术的优势； 2.）使用最先进的 艺术光学仪器可解析跨区域数千个特定类型单个神经元的动态 所有视觉皮层区域，表征区分可见知觉和不可见知觉的活动模式； 3）使用 化学遗传学操作通过抑制枕丘来测试感知机制，枕丘是皮质下区域， 调节视觉网络。这项工作的结果，作为初步数据的支持，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由 当前的理论。这将推动该领域达成数据驱动的共识，并阐明机制 有助于治疗疾病。