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.

项目概要 令人惊讶的是，在麻醉下或睡眠期间，初级感觉皮层中的单个神经元可靠地代表 感官信息，即使缺乏知觉10-13。这表明认知的崩溃 由于初级感觉系统无法有效地将其活动与其他皮质的活动整合起来 电路。一致地，知觉障碍，例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的扭曲4-7,14。然而，电路机制 允许将感觉信息与潜在神经活动整合的机制在很大程度上仍然未知。 自发的神经活动可以通过电生理学记录下来，并通过以下方式分类为“大脑状态”： 分解振荡模式15-17。在这里，我结合了神经生理学和光遗传学 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）的小鼠中进行的实验表明，简单的视觉刺激 引发复杂、可重复且高度相干的行进伽马波 (TGW)，几乎跨越整个区域 半皮质。我假设这些 TGW 存在于清醒和警惕的动物中，与 允许感知发生的特定且严格控制的传播模式。我将确定电路 光遗传学产生远程诱发 TGW 反应的机制。在这里，我将 使用两种麻醉剂异氟烷和氯胺酮，并自然地比较清醒状态下的视觉诱发活动 昏昏欲睡和药物麻醉的动物。异氟烷引发富含 δ 活性的光谱大脑状态 它模仿慢波睡眠，而氯胺酮则刺激伽马活性和其他特征 精神分裂症18-22。在目标 1 中，我将量化大脑光谱状态对视觉诱发 TGW 的影响 使用高密度表面皮层电图（ECoG）对小鼠皮层进行体内反应。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来自 视觉丘脑对于视觉诱发的、高度相干的 TGW 的生成和维持是必需的 振荡。总的来说，这项工作的结果将为理解感官如何发挥作用提供进一步的见解。 处理受到全局光谱大脑状态的影响。此外，我们的研究结果将告诉我们感官是如何被诱发的 活动与持续的皮质活动相结合，创造了感知可能或不可能的条件。 随后的见解也可能表明在行为状态期间感觉处理是如何改变的，例如 注意力不集中或睡眠，并可能揭示精神分裂症等疾病中知觉如何改变23。这 赠款还将为有抱负的临床科学家在优越的环境中提供不可或缺的支持 宾夕法尼亚大学佩雷​​尔曼医学院。她的最终职业目标是注入 将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。