CRCNS US-German Research Proposal: Origin of distributed modular activity in the neocortex

在大脑中，早期发育事件定义并限制了其未来的能力和功能。大规模的皮层网络对于大脑中的信息处理至关重要，但人们对这种网络在早期发育中是如何产生的知之甚少。该项目将通过创建跨学科合作来解决这个关键问题，该合作将开发并测试早期皮层神经活动的新型计算模型。这些模型旨在描述功能性神经网络在早期皮层中产生的机制，从而为大脑发育提供重要的新见解。此外，该项目将采用最先进的光学方法来测量和操纵发育中的皮层网络，为这些模型提供直接测试。该项目将产生新颖的计算工具和独特的早期大脑大规模成像数据集，这对广泛的科学界是有价值的，同时也为初级科学家提供理论和实验紧密结合的关键培训。总的来说，该项目将对功能性大脑发育的基本问题产生新的见解，并为未来的研究产生新的工具和数据集。灵长类动物和食肉动物的皮层活动是模块化的（柱状）和分布式的，连接着分布在皮层空间的功能单位。计算模型表明，这两个属性可以产生于早期发育皮层中的局部网络相互作用，但目前缺乏所提出的机制和实验验证的关键方面。为了解决这一关键的差距，在理解皮层网络的发展，这个项目将结合联合收割机计算建模与高灵敏度钙成像和药理学和光遗传学方法的上调和下调特定的电路组件。本研究将得出关键的预测模块和分布式皮质活动的局部网络组件的实验操作的影响，然后在体内进行这些操作，以测试所提出的机制的有效性。这项工作将大大加深对早期发育皮层中模块化和分布式活动起源的理解，同时通过识别产生模块化活动的皮层机制并测试远程网络相关性是否可以从局部循环连接中产生，从而解决该领域长期存在的问题。通过结合最先进的实验方法，数据分析和理论建模，该项目将产生一个定量的了解机制，使年轻的大脑皮层活动的两个最突出的特点。德国联邦教育和研究部（BMBF）正在资助一个配套项目。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In the brain, early developmental events define and constrain its future capabilities and functions. Large-scale cortical networks are critical to the processing of information in the brain, yet very little is known about how such networks arise in early development. This project will address this critical question by creating an interdisciplinary collaboration that will develop and then test novel computational models of neural activity in the early cortex. These models will aim to describe the mechanisms through which functional neural networks arise in the early cortex, thereby providing critical new insights into brain development. Furthermore, this project will employ cutting edge optical approaches to measure and manipulate networks in the developing cortex, providing a direct test of these models. This project will produce novel computational tools and unique large-scale imaging datasets of the early brain that will be valuable to the broad scientific community, while also providing key training for junior scientists in the tight integration of theory and experiment. Collectively, this project will yield new insights into fundamental questions of functional brain development and generate novel tools and datasets for future research. Cortical activity in primates and carnivores is both modular (columnar) and distributed, linking functional units that are spread across cortical space. Computational models suggest that these two properties can arise from local network interactions in the early developing cortex, however both critical aspects of the proposed mechanisms and experimental validation are currently lacking. In order to address this key gap in the understanding of cortical network development, this project will combine computational modeling with highly sensitive calcium imaging and pharmacological and optogenetic methods for up-and down-regulating specific circuit components. This research will derive critical predictions for the effects of experimental manipulations of local network components on modular and distributed cortical activity and then perform these manipulations in vivo to test the validity of the proposed mechanisms. This work will greatly deepen the understanding of the origin of modular and distributed activity in the early developing cortex, while addressing long-standing issues in the field by identifying the cortical mechanism for generating modular activity and testing whether long-range network correlations can arise from local recurrent connections as a truly emergent property. By combining state of the art experimental approaches, data analysis, and theoretical modeling, this project will yield a quantitative understanding of the mechanisms that give rise in the young brain to two of the most prominent features of cortical activity. A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.