Self-organization of modular network architecture by activity-dependent neuronal migration and outgrowth

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Abstract

The spatial distribution of neurons and activity-dependent neurite outgrowth shape long-range interaction, recurrent local connectivity and the modularity in neuronal networks. We investigated how this mesoscale architecture develops by interaction of neurite outgrowth, cell migration and activity in cultured networks of rat cortical neurons and show that simple rules can explain variations of network modularity. In contrast to theoretical studies on activity-dependent outgrowth but consistent with predictions for modular networks, spontaneous activity and the rate of synchronized bursts increased with clustering, whereas peak firing rates in bursts increased in highly interconnected homogeneous networks. As Ca²⁺ influx increased exponentially with increasing network recruitment during bursts, its modulation was highly correlated to peak firing rates. During network maturation, long-term estimates of Ca²⁺ influx showed convergence, even for highly different mesoscale architectures, neurite extent, connectivity, modularity and average activity levels, indicating homeostatic regulation towards a common set-point of Ca²⁺ influx.

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All data generated or analysed during this study are included in the manuscript and supporting files. Matlab code and source data files have been provided for Figures 3-6.

Article and author information

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Samora Okujeni

Department of Microsystems Engineering, Faculty of Engineering, University of Freiburg, Freiburg, Germany

For correspondence
samora.okujeni@biologie.uni-freiburg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7924-3651
Ulrich Egert

Department of Microsystems Engineering, Faculty of Engineering, University of Freiburg, Freiburg, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4583-0425

Funding

Deutsche Forschungsgemeinschaft (EXC 1086)

Ulrich Egert

Bundesministerium für Bildung und Forschung (FKZ 01GQ0420)

Ulrich Egert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal handling and tissue preparation were done in accordance with the guidelines for animal research at the University of Freiburg and approved by the Regierungspräsidium Freiburg (permits X-12/08D, X-16/07A, X-15/01H, X-18/04K).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.