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.

项目总结 大脑对感觉信息的感知高度依赖于信息上下文，其中 对信息量最大或“新奇”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，用于自动聚焦到信息量最大的刺激。研究使用了 脑电和脑磁图的奇怪范式表明，新奇检测缺陷出现在 精神分裂症，表明它对正常的信息处理和认知功能具有很高的重要性。因为 这些方法固有的低分辨率，是新颖性检测背后的神经元电路机制 仍然难以捉摸。在这个项目中，我将被训练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，以学习作为新颖性检测基础的群体活动， 并与大脑皮层交互以操纵上下文决策和印记改进的检测 新奇。 首先，(目标1)我将使用双光子全息钙成像来记录数百个神经元 同时在清醒的老鼠身上进行新奇的检测任务。新颖性检测的单次试验轨迹 将提取神经元，以了解种群真正的高维活动结构，并揭示 正在进行的内部动力学影响感官诱发反应。此外，由于新颖性检测 分解成预先注意和注意力依赖的成分，我们将训练小鼠进行新奇检测 行为任务，以阐明个体的试验轨迹如何与注意力和知觉相关。最后，我们会 在精神分裂症的小鼠模型上重复这些实验，以揭示正在进行的活动和刺激是如何引起的 单项试验反应在疾病表型中受到影响。 在这个项目的第二部分(目标2)，我们将使用尖端的双光子全息方法来 与大脑交互，在新颖性检测过程中操纵感知和控制行为输出 行为举止令人厌烦。最后，我们将用全息的“训练”方法，将更强的新奇检测电路印在 试图挽救精神分裂症模型小鼠的疾病表型。 这些研究将产生1)真正的高维神经活动，潜在的新颖性检测以及它是如何 取决于正在进行的巡回活动，ii)对如何引发单项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)是否可能使用全息训练的新颖性 检测电路可提高刺激诱发反应和抢救疾病表型。这项工作将提供 在光学、大规模录音和神经活动操纵方面有丰富专业知识的候选人，以及 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。