Holographic imprinting of novelty detection in mice

小鼠新颖性检测的全息印记

• 批准号: 10023434
• 负责人: Yuriy Shymkiv
• 金额: $ 4.55万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10023434
• 关键词: 3-Dimensional; Affect; Attention; Auditory; Behavior; Behavior Control; Behavioral; Biological Markers; Brain; Calcium; Cells; Chronic; Data; Decision Making; Detection; Electroencephalography; Environment; Event-Related Potentials; Functional disorder; Future; Generations; Ii-Key; Image; Impaired cognition; Individual; Learning; Light; Link; Measures; Mental disorders; Methods; Modeling; Mus; Neurons; Optics; Output; Patients; Pattern; Perception; Play; Population; Population Dynamics; Positioning Attribute; Resolution; Role; Schizophrenia; Sensory; Stimulus; Structure; Symptoms; Testing; Therapeutic; Training; Visual; Work; awake; career; cognitive function; disease phenotype; experimental study; high dimensionality; holographic stimulation; imprint; improved; information processing; insight; large datasets; mouse model; neural circuit; neuronal circuitry; novel; novelty processing; optogenetics; relating to nervous system; response; sensory cortex; two-photon

PROJECT SUMMARY Perception of sensory information by the brain is highly dependent on the information context, where responses to the most informative, or “novel”, stimuli are selectively amplified. Novelty detection occurs early in the sensory cortex and is used for automatic focusing to stimuli that are most informative. Studies using the oddball paradigm with EEG and MEG show that deficits of novelty detection appear in patients with schizophrenia, suggesting its high importance for normal information processing and cognitive function. Because these methods are inherently low resolution, the neuronal circuit mechanism underlying novelty detection remains elusive. In this project I will be trained to use the Spatial Light Modulator for i) 3D volumetric two-photon calcium imaging, and ii) holographic optogenetics, to learn the population activity underlying novelty detection, and to interface with the cortex to manipulate contextual decision making and imprinting improved detection of novelty. First, (AIM 1) I will use two-photon holographic calcium imaging to record from hundreds of neurons simultaneously in awake mice undergoing a novelty detection task. Single trial trajectories of novelty detection neurons will be extracted to learn the true high dimensional activity structure of the population, and reveal how ongoing internal dynamics affect the sensory evoked response. Additionally, since novelty detection decomposes into preattentive and attention dependent components, we will train mice in a novelty detection behavior task to elucidate how individual trial trajectories correlate to attention and perception. Finally, we will repeat these experiments in a mouse model of schizophrenia, to reveal how ongoing activity and stimulus evoked single trial responses are affected in the disease phenotype. In the second part of this project (AIM 2) we will use cutting edge two-photon holographic methods for interfacing with the brain, to manipulate perception and control behavioral output during novelty detection behavior taks. Finally, we will use holographic “training” methods to imprint stronger novelty detection circuits in schizophrenia model mice in an attempt to rescue the disease phenotype. These studies will yield i) true high dimensional neural activity underlying novelty detection and how it depends on the ongoing circuit activity, ii) key insights of how evoked single trial dynamics and ongoing activity is disrupted in the schizophrenia model, and iii) whether it is possible to use holographic training of novelty detection circuits to improve stimulus evoked response and rescue the disease phenotype. This work will provide the candidate with strong expertise in optics, large scale recordings and manipulation of neural activity, and analysis of neural circuit data, position him to pursue wide range of topics and tackle challenging question in the future career.

项目摘要 大脑对感官信息的感知高度取决于信息上下文 对最有用或“新颖”刺激的响应有选择地放大。新颖性检测发生在早期 感觉皮层，用于自动聚焦，以刺激最有用的刺激。使用 与脑电图和梅格的ODBall范式显示，定义了患者的新颖性检测外观 精神分裂症，表明其对正常信息处理和认知功能的重要性很高。因为 这些方法本质上是低分辨率，即新颖性检测的神经元电路机制 仍然难以捉摸。在这个项目中，我将接受培训，可以使用空间光调节器i）3D体积二光子 钙成像和ii）全息光遗传学，以学习新颖性检测的种群活动， 并与皮层接触以操纵上下文决策并改进发现 新奇。 首先，（AIM 1）我将使用两光子全息钙成像记录数百个神经元 简单的清醒老鼠执行了新颖的检测任务。单一试验轨迹的新颖轨迹 将提取神经元以学习人群的真实高维活动结构，并揭示如何 持续的内部动力学会影响感官诱发的响应。此外，由于新颖性检测 分解成浓度和注意力依赖的组件，我们将在新颖的检测中训练小鼠 行为任务以阐明单个试验轨迹如何与注意力和感知相关联。最后，我们会的 在精神分裂症的小鼠模型中重复这些实验，以揭示持续的活动和刺激如何唤起 单个试验反应在疾病表型中受到影响。 在该项目的第二部分中（AIM 2），我们将使用最前沿的两光全息方法 与大脑接口，以操纵感知和控制新颖性检测期间的行为输出 行为提取。最后，我们将使用全息“培训”方法在 精神分裂症模型小鼠试图营救疾病表型。 这些研究将产生i）真正的高维神经活动基础的新颖性检测以及它如何 取决于正在进行的电路活动，ii）唤起单个试验动态和持续活动的关键见解 在精神分裂症模型中被破坏，iii）是否可以使用新颖性训练 检测电路改善刺激诱发了反应并挽救了疾病表型。这项工作将提供 具有强大专业知识的候选人在光学，大规模记录和对神经活动的操纵以及 分析神经电路数据，将他定位为在 未来职业。