Quantifying the effect of brain state on the spatiotemporal dynamics of visual evoked responses

量化大脑状态对视觉诱发反应时空动态的影响

• 批准号: 10021403
• 负责人: Adeeti Aggarwal
• 金额: $ 3.27万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021403
• 关键词: Action Potentials; Affect; Anesthesia procedures; Anesthetics; Animals; Area; Attention; Behavioral; Brain; Cell Nucleus; Characteristics; Clinical Medicine; Complex; Development; Disease; Drowsiness; Electrocorticogram; Electrophysiology (science); Environment; Fostering; Generations; Goals; Grant; Implant; Individual; Interneurons; Intuition; Isoflurane; Ketamine; Light; Maintenance; Modality; Mus; Neurons; Neurosciences; Pathology; Pattern; Pennsylvania; Perception; Perceptual Disorders; Pharmacology; Phase; Physiology; Process; Property; Reproducibility; Research; Resistance; Sampling; Schizophrenia; Scientist; Sensory; Sleep; Slice; Slow-Wave Sleep; Source; Stimulus; Surface; Thalamic structure; Travel; Universities; Visual; Visual Perception; Visual evoked cortical potential; Visual system structure; Wakefulness; Work; area striata; association cortex; autism spectrum disorder; awake; base; career; density; doctoral student; experimental study; extrastriate; in vivo; inattention; insight; medical schools; millimeter; neurophysiology; optogenetics; relating to nervous system; response; sensory cortex; sensory integration; sensory system; spatiotemporal; visual processing; visual stimulus

PROJECT SUMMARY Surprisingly, under anesthesia or during sleep, individual neurons in primary sensory cortices reliably represent sensory information, even when perception is absent10–13. This suggests that the breakdown of perception is due to an inability of the primary sensory system to effectively integrate its activity with that of other cortical circuits. Consistently, disorders of perception, such as schizophrenia and autism, are associated with distortions in the spatial and temporal integration of sensory-evoked activity4–7,14. Yet, the circuit mechanisms that allow for integration of sensory information with the underlying neural activity remain largely unknown. Spontaneous neural activity can be recorded with electrophysiology and classified into “brain states” by decomposing the oscillatory patterns15–17. Herein, I deploy a combination of neurophysiology and optogenetics to quantify the salient features of spatiotemporal responses elicited by visual stimuli. Our preliminary experiments in mice implanted with high density electrocorticography (ECoG) show that simple visual stimuli elicit complex, reproducible, and highly coherent traveling gamma waves (TGW) that span nearly an entire hemicortex. I hypothesize that these TGWs, present in the awake and vigilant animal, are associated with specific and tightly controlled pattern of propagation that permit perception to occur. I will determine circuit mechanisms underlying the generation of long-range evoked TGW responses with optogenetics. Here, I will utilize two anesthetic agents, isoflurane and ketamine, and compare visual evoked activity in awake, naturally drowsy, and pharmacologically anesthetized animals. Isoflurane elicits spectral brain states rich in delta activity which mimic slow wave sleep, while ketamine stimulates gamma activity and other features present in schizophrenia18–22. In Aim 1, I will quantify the brain spectral state dependent effect on visual evoked TGW responses in mouse cortex in vivo using high density surface electrocorticography (ECoG). In Aim 2, I will quantify the effect of brain state on the laminar spatiotemporal organization of these visual responses, using multiple multichannel depth probes. In Aim 3, I will use optogenetics to determine whether projections from the visual thalamus are necessary for the generation and maintenance of visual evoked, highly coherent TGW oscillations. Collectively, the results of this work will provide further insights to understanding how sensory processing is affected by the global spectral brain state. Moreover, our findings will inform how sensory evoked activity integrates with ongoing cortical activity to create conditions in which perception is and is not possible. The ensuing insights may also suggest how sensory processing is altered during behavioral states such as inattention or sleep, and may shed light on how perception is altered in diseases such as schizophrenia23. This grant will also provide indispensable support for an aspiring clinician scientist in an outstanding environment at the University of Pennsylvania, Perelman School of Medicine. Her ultimate career goals are to infuse fundamental neuroscience into clinical medicine to better understand healthy and disease states.

项目摘要 令人惊讶的是，在麻醉或睡眠期间，初级感觉皮层中的单个神经元可靠地代表了 感官信息，即使感知是缺席10 -13。这表明，知觉的崩溃是 由于初级感觉系统不能有效地将其活动与其他皮质的活动整合， 电路.同样，知觉障碍，如精神分裂症和自闭症，与 感觉诱发活动的空间和时间整合失真4 - 7，14.然而，电路机制 使感觉信息与潜在的神经活动相结合的机制在很大程度上仍然是未知的。 自发的神经活动可以用电生理学记录，并通过以下方式分类为“大脑状态”： 分解振荡模式15 -17.在此，我将神经生理学和光遗传学相结合， 量化视觉刺激引起的时空反应的显着特征。我们的初步 在植入高密度皮层电图（ECoG）的小鼠中的实验表明，简单的视觉刺激 引发复杂的，可重复的，高度相干的行波伽马波（TGW），跨越几乎整个 半皮质我假设这些存在于清醒和警惕的动物中的TGW与 允许感知发生的特定且严格控制的传播模式。我将决定电路 利用光遗传学研究了长距离诱发TGW反应产生的潜在机制。来，我来 使用两种麻醉剂，异氟醚和氯胺酮，并比较清醒，自然 昏昏欲睡的，被麻醉的动物。异氟烷激发富含δ活性的光谱脑状态 它模仿慢波睡眠，而氯胺酮刺激伽马活动和其他特征， 精神分裂症18 -22在目标1中，我将量化视觉诱发TGW的脑光谱状态依赖效应 使用高密度表面皮层电描记术（ECoG）在体内小鼠皮层中的反应。在目标2中，我将 量化大脑状态对这些视觉反应的层状时空组织的影响，使用 多个多通道深度探头。在目标3中，我将使用光遗传学来确定是否从 视丘脑是产生和维持视觉诱发的高度连贯的TGW所必需的 振荡总的来说，这项工作的结果将提供进一步的见解，以了解如何感官 处理受到全局谱脑状态的影响。此外，我们的发现将告知感官如何诱发 活动与正在进行的皮层活动相结合，以创造感知是可能的和不可能的条件。 随后的见解也可能表明感觉处理在行为状态下是如何改变的， 注意力不集中或睡眠，并可能揭示如何感知改变的疾病，如精神分裂症23。这 格兰特还将提供一个有抱负的临床科学家在一个优秀的环境中不可或缺的支持， 宾夕法尼亚大学佩雷尔曼医学院她的最终职业目标是 基础神经科学融入临床医学，以更好地了解健康和疾病状态。