Holographic imprinting of novelty detection in mice

小鼠新颖性检测的全息印记

• 批准号: 9910718
• 负责人: Yuriy Shymkiv
• 金额: $ 4.5万
• 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/9910718
• 关键词: 3-Dimensional; Affect; Attention; Auditory; Behavior; Behavior Control; Behavioral; Biological Markers; Brain; Calcium; Cells; Chronic; Data; Data Set; 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; imprint; improved; information processing; insight; 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.

项目概要 大脑对感官信息的感知高度依赖于信息背景，其中 对信息最丰富或“新颖”的刺激的反应会被选择性地放大。新颖性检测发生在早期 感觉皮层，用于自动聚焦信息最丰富的刺激。研究使用 脑电图和脑磁图的奇怪范式表明，患有以下疾病的患者出现新颖性检测缺陷 精神分裂症，表明它对正常信息处理和认知功能非常重要。因为 这些方法本质上是低分辨率的，神经元电路机制是新颖性检测的基础 仍然难以捉摸。在这个项目中，我将接受培训，使用空间光调制器来实现 i) 3D 体积双光子 钙成像，以及 ii) 全息光遗传学，以了解新奇检测背后的群体活动， 并与皮层交互以操纵上下文决策并印记改进的检测 新奇。 首先，（AIM 1）我将使用双光子全息钙成像来记录数百个神经元 同时在清醒的小鼠中进行新奇检测任务。新颖性检测的单次试验轨迹 将提取神经元以了解群体的真实高维活动结构，并揭示如何 持续的内部动态影响感官诱发反应。此外，由于新颖性检测 分解为前注意和注意力依赖成分，我们将训练小鼠进行新奇检测 行为任务来阐明个体试验轨迹如何与注意力和感知相关。最后，我们将 在精神分裂症小鼠模型中重复这些实验，以揭示持续的活动和刺激是如何引起的 单次试验反应会受到疾病表型的影响。 在该项目的第二部分（AIM 2）中，我们将使用尖端的双光子全息方法 与大脑交互，在新颖性检测期间操纵感知并控制行为输出 行为需要。最后，我们将使用全息“训练”方法在其中印上更强的新颖性检测电路 精神分裂症模型小鼠试图挽救该疾病表型。 这些研究将产生 i) 新颖性检测背后的真实高维神经活动及其如何进行 取决于正在进行的循环活动，ii) 关于如何诱发单次试验动态和正在进行的活动的关键见解 在精神分裂症模型中被破坏，以及iii）是否可以使用新奇的全息训练 检测电路以改善刺激诱发反应并挽救疾病表型。这项工作将提供 候选人在光学、大规模记录和神经活动操纵方面拥有丰富的专业知识，并且 分析神经回路数据，使他能够追求广泛的主题并解决具有挑战性的问题 未来的职业生涯。