Holographic imprinting of novelty detection in mice

项目摘要 大脑对感官信息的感知高度依赖于信息背景， 对信息量最大或“新颖”的刺激的反应被选择性地放大。新奇检测发生在 感觉皮层，用于自动聚焦于信息量最大的刺激。研究使用 脑电图和脑磁图的oddball范式显示， 精神分裂症，表明其对正常信息处理和认知功能的高度重要性。因为 这些方法固有地是低分辨率的，作为新奇检测基础的神经元电路机制 仍然难以捉摸在这个项目中，我将接受培训，使用空间光调制器i）3D体积双光子 钙成像，和ii）全息光遗传学，以了解新奇检测背后的群体活动， 并与皮层接口，以操纵上下文决策和印记， 新奇 首先，（AIM 1）我将使用双光子全息钙成像记录数百个神经元 同时在清醒的小鼠进行新奇检测任务。新奇检测的单次试验轨迹 神经元将被提取，以了解人口的真正高维活动结构，并揭示如何 持续的内部动力学影响感觉诱发反应。此外，由于新奇检测 分解为前注意和注意依赖成分，我们将训练小鼠进行新奇检测， 行为任务，以阐明个人的审判轨迹如何与注意力和感知相关。最后我们将 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是如何诱发 单次试验应答在疾病表型中受到影响。 在这个项目的第二部分（AIM 2）中，我们将使用最先进的双光子全息方法， 与大脑接口，以操纵感知并控制新奇检测期间的行为输出 行为需要。最后，我们将使用全息“训练”方法，在大脑中植入更强的新奇检测电路。 精神分裂症模型小鼠，试图挽救疾病表型。 这些研究将产生i）真实的高维神经活动，其基础是新奇检测以及它如何 取决于正在进行的电路活动，ii）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）是否可能使用新奇的全息训练 检测电路，以改善刺激诱发的反应和挽救疾病表型。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具有很强的专业知识， 神经电路数据的分析，定位他追求广泛的主题和解决具有挑战性的问题， 未来的职业。

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.