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

在大脑中，早期发育事件定义和限制了它未来的能力和功能。大规模的大脑皮层网络对大脑中的信息处理至关重要，但人们对这种网络是如何在早期发育过程中产生的知之甚少。这个项目将通过创建一个跨学科的合作来解决这个关键问题，该合作将开发并测试早期皮质神经活动的新计算模型。这些模型将旨在描述功能神经网络在早期皮质中产生的机制，从而为大脑发育提供关键的新见解。此外，该项目将使用尖端光学方法来测量和操纵发育中的大脑皮层网络，提供对这些模型的直接测试。该项目将产生新的计算工具和独特的早期大脑大规模成像数据集，这将对广泛的科学界有价值，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。总而言之，该项目将对大脑功能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。灵长类和食肉动物的皮质活动既是模块化的(柱状)，也是分布的，连接分布在皮质空间的功能单位。计算模型表明，这两个特性可以产生于早期发育皮层的局部网络相互作用，然而，所提出的机制的关键方面和实验验证目前都缺乏。为了解决在理解皮质网络发育方面的这一关键差距，该项目将结合计算建模和高灵敏钙成像以及上调和下调特定电路组件的药理学和光遗传学方法。这项研究将得出对局部网络组件的实验性操作对模块化和分布式皮质活动的影响的关键预测，然后在活体中执行这些操作来测试所提出的机制的有效性。这项工作将极大地加深对早期发育皮质中模块和分布活动起源的理解，同时通过确定产生模块活动的皮质机制并测试是否可以从局部反复连接中产生远程网络关联作为真正的紧急性质来解决该领域的长期问题。通过将最先进的实验方法、数据分析和理论建模相结合，该项目将对导致年轻大脑中两个最显著的皮质活动特征的机制产生定量的理解。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智力优势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.