CRCNS: US-German Res Prop: The Role of Spontaneous Activity in Cortical Development

CRCNS：美国-德国 Res Prop：自发活动在皮质发育中的作用

• 批准号: 9335859
• 负责人: DAVID FITZPATRICK
• 金额: $ 22.88万
• 依托单位: MAX PLANCK FLORIDA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9335859
• 关键词: Address; Animals; Back; Biological Models; Calcium; Chronic; Collaborations; Communities; Computer Simulation; Data; Data Analyses; Development; Educational process of instructing; Event; Exhibits; Eye; Ferrets; Florida; General Population; German population; Goals; High School Student; Image; Individual; Institutes; Journals; Knowledge; Learning; Light; Maps; Measures; Methodology; Methods; Modeling; Monitor; Nature; Neurodevelopmental Disorder; Neurons; Pattern; Population; Publications; Quality of life; Research; Research Activity; Research Personnel; Resolution; Role; Sensory; Shapes; Side; Stimulus; Structure; Techniques; Testing; Theoretical model; Time; Ursidae Family; Visual; Visual Cortex; activity marker; base; course development; data modeling; improved; in vivo imaging; insight; mathematical model; mature animal; neural patterning; novel; orientation columns; orientation selectivity; outreach; programs; relating to nervous system; response; scaffold; sensor; spatiotemporal; symposium; synergism; theories; tool; undergraduate student; visual stimulus; web site

DESCRIPTION (provided by applicant): The goal of the proposed research is to understand the role of spontaneous activity in early cortical development. The cortex is spontaneously active from the first moments when circuits form. However, so far we know only very little about the patterns of spontaneous activity in the early cortex and very few models have addressed their role in shaping its circuitry. An experimental neuroscientist from the Max Planck Florida Institute (MPFI) is teaming up with a computational neuroscientist from the Frankfurt Institute of Advance Studies (FIAS) to shed new light on this important issue. Our central hypothesis is that early spontaneous patterns of activity exhibit an orderly columnar structure that forms the basis for building sensory evoked representations. Using the orientation preference map in ferret visual cortex as a model system, the team will employ novel techniques for expressing highly sensitive and persistent neural activity markers in visual cortex to perform chronic imaging of spontaneous and visually-evoked activity of large populations of neurons, starting a week prior to orientation map formation, up to its full maturation several weeks later. Using quantitative analysis of patterns of spontaneous activity, the team will characterize the structure of spontaneous activity in the early visual cortex and describe its relation to the mature orientation preference map. Constrained by the empirical results, a mathematical model will be built, aiming at providing a concise and accurate description of our spontaneous activity scaffolding hypothesis and to derive testable implications of this hypothesis. Through this project the researchers are expected to gain a quantitative understanding of how spontaneous and visually-driven activity interact to shape the early development of cortical circuitry. The research proposed here is expected to result in an improved understanding of early cortical development. Spontaneous activity potentially has a huge impact on developing cortical circuits and the proposed research aims at elucidating its role. It could reveal a previously unappreciated potential supporting role of spontaneous activity in forming sensory representations during early cortical development. Methodologically, the project will establish new experimental techniques that allow monitoring with unprecedented sensitivity the activity of large populations of neurons over extended periods of time, beginning at very early stages in development. It will provide novel methods for quantifying the spatiotemporal patterns of spontaneous and visual evoked population activity. Scientifically, the study will highlight the unanticipated richness and modular organization of early spontaneous activity in the cortex. In addition, the project will establish a new theory of visual cortical development that explicitly takes the rich nature of spontaneous activity into account. This theory will be strongly backed up by the empirical data. Beyond the new insights that will be gained about cortical development, the proposed research will have a broader impact in demonstrating the synergy that derives from combining state of the art experimental approaches, with novel techniques for data analysis and theoretical modeling. This project creates an interdisciplinary US-German collaboration between the FIAS and the MPFI. The results of this project will be broadly disseminated to the research community in journal publications, at conferences, and via a project website, and to the general public through presentations, outreach events and unique programs on both sides. Teaching and learning is promoted through programs for graduate, undergraduate, and high school students as well as engagement of post-baccalaureate participation in research activities. Finally, this project will contribute to a deeper understanding of the activity-dependent mechanisms that are responsible for the normal development of cortical circuits - fundamental knowledge that serves as the basis for novel treatments for a host of neurodevelopmental disorders that impact the quality of life for billions of people worldwide.

描述（由申请人提供）：拟议研究的目标是了解自发活动在早期皮质发育中的作用。大脑皮层从回路形成的第一时刻起就自发地活跃起来。然而，到目前为止，我们对早期皮层的自发活动模式知之甚少，也很少有模型讨论它们在塑造其电路中的作用。来自马克斯·普朗克佛罗里达研究所（MPFI）的一位实验神经科学家正在与来自法兰克福高级研究所（FIAS）的一位计算神经科学家合作，为这个重要问题提供新的见解。我们的中心假设是，早期的自发活动模式表现出有序的柱状结构，形成了建立感官诱发表征的基础。使用雪貂视觉皮层中的方向偏好图作为模型系统，该团队将采用新技术在视觉皮层中表达高度敏感和持久的神经活动标记，以执行大量神经元的自发和视觉诱发活动的慢性成像，从方向图形成前一周开始，直到几周后完全成熟。通过对自发活动模式的定量分析，研究小组将描述早期视觉皮层自发活动的结构，并描述其与成熟方向偏好图的关系。在实证结果的约束下，建立一个数学模型，旨在提供一个简洁和准确的描述我们的自发活动支架假说，并得出该假说的可检验的含义。通过这个项目，研究人员有望定量了解自发和视觉驱动的活动如何相互作用，以塑造皮层电路的早期发展。 这里提出的研究有望提高对早期皮质发育的理解。自发活动可能对大脑皮层回路的发育产生巨大影响，这项研究旨在阐明其作用。它可以揭示一个以前未被重视的潜在的支持作用，自发活动在形成早期皮层发育过程中的感觉表征。从方法上讲，该项目将建立新的实验技术，以前所未有的灵敏度监测大量神经元在很长一段时间内的活动，从发育的早期阶段开始。它将提供新的方法来量化自发和视觉诱发的群体活动的时空模式。从科学的角度来看，这项研究将突出大脑皮层早期自发活动的意外丰富性和模块化组织。此外，该项目将建立一个新的视觉皮层发展理论，明确考虑到自发活动的丰富性质。这一理论将得到经验数据的有力支持。除了将获得关于皮质发育的新见解之外，拟议的研究将在展示最先进的实验方法与数据分析和理论建模的新技术相结合所产生的协同作用方面产生更广泛的影响。 该项目在FIAS和MPFI之间建立了跨学科的美德合作。该项目的成果将通过期刊出版物、会议和项目网站向研究界广泛传播，并通过双方的演示、外联活动和独特方案向公众传播。教学和学习是通过研究生，本科生和高中学生的计划，以及参与研究活动的学士后参与促进。最后，该项目将有助于更深入地了解负责皮层回路正常发育的活动依赖性机制-基础知识，这些基础知识将成为影响全球数十亿人生活质量的许多神经发育障碍的新治疗方法的基础。