Traveling waves in neocortical circuits: Mechanisms, computational roles in sensory processing, and impact on sensory perception

新皮质回路中的行波：感觉处理中的机制、计算作用以及对感觉知觉的影响

• 批准号: 10655101
• 负责人: Todd P Coleman
• 金额: $ 247.84万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-31 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655101
• 关键词: Affect; Anatomy; Animals; Area; Behavior; Brain; Callithrix; Cells; Cognition; Cognitive; Color; Communication; Custom; Data; Data Scientist; Detection; Dorsal; Electrocorticogram; Electrodes; Electrophysiology (science); Equilibrium; Fiber; Fluorescence; Future; Goals; Image; Interneurons; Kinetics; Learning; Link; Measurement; Measures; Methods; Modeling; Monkeys; Mus; Nature; Neocortex; Neurons; Neurosciences; Neurosciences Research; Optics; Outcome; Pattern; Perception; Population; Process; Research; Resolution; Role; Scientist; Sensory; Signal Transduction; Statistical Data Interpretation; Stimulus; Structure; Surface; Syncope; System; Techniques; Testing; Theoretical model; Travel; Visual; Visual Cortex; Visual Perception; adjudication; area MT; awake; brain research; brain shape; cell type; empowerment; experimental study; extrastriate visual cortex; imaging approach; imaging study; improved; innovation; insight; invention; motor behavior; motor control; neocortical; network models; neural; neural patterning; neuroimaging; neurophysiology; neurotransmission; new technology; nonhuman primate; novel; optical imaging; predictive modeling; response; retinotopic; spatiotemporal; temporal measurement; tool; visual stimulus; voltage; voltage sensitive dye

PROJECT SUMMARY/ABSTRACT An important longstanding goal in neuroscience research is to understand how large-scale spatiotemporal patterns of neural activity emerge in the brain and whether they have a direct role in shaping the brain’s computational processes and thereby mammalian behavior. Notably, traveling waves of neural activity have been implicated in sensory, cognitive, and motor behaviors, and this team recently found that intrinsic traveling waves (iTWs) in visual cortical areas predict the magnitude of evoked spiking activity and visual perceptual sensitivity in awake, behaving non-human primates. However, it remains unclear whether iTWs reflect an underlying fundamental mechanism of cortical function or whether they might simply be epiphenomenal. This project will examine the role of neocortical iTWs in visual perception and is guided by a theoretical model of iTW activity that makes specific testable and falsifiable predictions about the mechanisms that give rise to the spatiotemporal features of iTWs and their roles in sensory behavior. The model is based on a network of spiking neurons and predicts that iTWs emerge from the anatomical organization of horizontal cortical fibers and result in shifts in the balance of excitatory (E) and inhibitory (I) population activity that travel as waves, The model further predicts that iTWs are retinotopically coordinated across visual cortical areas, and that this coordination is the mechanism by which iTWs improve perception. However, these predictions could be wrong. Empirical tests of the model’s predictions will require activity measurements from specific neuron-types, across wide fields- of-view, and with excellent spatial and temporal resolution in awake behaving animals. To perform such measurements, the team recently invented several new technologies: (1) genetically encoded fluorescent voltage indicators (GEVIs) that they will target to specific E or I neural populations; (2) a custom-built dual-color fluorescence mesoscope to track the subthreshold population voltage dynamics of 2 neuron-types at once, across a 8-mm field-of-view spanning multiple cortical areas in marmoset and mouse cortex; (3) transparent electrode arrays that allow measurements of LFPs to be performed across the cortex concurrently with voltage imaging studies of E and I population activity; (4) transparent laminar electrode arrays to measure the spiking activity of cells across the different cortical layers. By combining the use of these four innovations in marmosets and mice performing a visual detection task, the team will test the predictions of the theoretical model and learn how different cortical neuron-types impact iTW dynamics and perceptual sensitivity. Aim 1 tests the hypothesis that E/I population activity travels as iTWs in mice and marmosets. Aim 2 tests the prediction that iTWs are coordinated retinotopically across cortical areas, and that this coordination enhances perceptual sensitivity. Aim 3 will account mechanistically for the results of Aims 1 and 2 in a theoretically grounded spiking network model. Overall, by using innovative new technologies this interdisciplinary team will provide key insights into longstanding conceptual issues of profound importance to brain research.

项目概要/摘要 神经科学研究的一个重要的长期目标是了解大规模时空如何 大脑中出现的神经活动模式以及它们是否在塑造大脑的过程中具有直接作用 值得注意的是，神经活动的行波已经改变了计算过程，从而影响了哺乳动物的行为。 与感觉、认知和运动行为有关，该团队最近发现内在旅行 视觉皮层区域中的波（iTW）预测诱发的尖峰活动和视觉感知的强度 然而，目前还不清楚 iTW 是否反映了清醒、有行为的非人类灵长类动物的敏感性。 皮质功能的潜在基本机制，或者它们是否可能只是附带现象。 该项目将研究新皮质 iTW 在视觉感知中的作用，并以理论模型为指导 iTW 活动对引起 iTW 的时空特征及其在感觉行为中的作用该模型基于尖峰网络。 神经元并预测 iTWs 从水平皮质纤维的解剖组织中出现并产生结果 以波浪形式传播的兴奋性 (E) 和抑制性 (I) 群体活动的平衡变化，该模型 进一步预测 iTW 在视觉皮层区域之间进行视网膜局部协调，并且这种协调 是 iTW 改善感知的机制。但是，这些预测可能是错误的。 模型预测的测试将需要跨广泛领域的特定神经元类型的活动测量 视野外，并且在清醒行为的动物中具有出色的空间和时间分辨率。 为了进行此类测量，该团队最近发明了几项新技术：（1）基因编码 荧光电压指示器 (GEVI)，它们将针对特定的 E 或 I 神经群体 (2) 定制的； 双色荧光介观镜可跟踪 2 种神经元类型的阈下群体电压动态 (3) 一次，跨越狨猴和小鼠皮层多个皮层区域的 8 毫米视野； 透明电极阵列，允许同时在皮层上进行 LFP 测量 对 E 和 I 群体活动进行电压成像研究；(4) 透明层状电极阵列进行测量 通过结合使用这四种创新，不同皮质层细胞的尖峰活动。 狨猴和小鼠执行视觉检测任务，团队将测试理论模型的预测 并了解不同的皮质神经元类型如何影响 iTW 动力学和感知灵敏度。 目标 1 测试了 E/I 群体活动在小鼠和狨猴中以 iTW 形式传播的假设，目标 2 测试了这一假设。 预测 iTWs 在整个皮质区域的视网膜局部进行协调，并且这种协调增强了 目标 3 将在理论上机械地解释目标 1 和 2 的结果。 总体而言，通过使用创新的新技术，这个跨学科团队将实现接地尖峰网络模型。 为对大脑研究具有深远意义的长期概念问题提供关键见解。