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

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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.