Homophilic wiring principles underpin neuronal network topology in vitro
- University of Cambridge, United Kingdom
- ETH Zurich, Switzerland
- F. Hoffmann-La Roche Ltd, Switzerland
- Harvard Medical School, United States
Abstract
Economic efficiency has been a popular explanation for how networks self-organize within the developing nervous system. However, the precise nature of the economic negotiations governing this putative organizational principle remains unclear. Here, we address this question further by combining large-scale electrophysiological recordings, to characterize the functional connectivity of developing neuronal networks in vitro, with a generative modeling approach capable of simulating network formation. We find that the best fitting model uses a homophilic generative wiring principle in which neurons form connections to other neurons which are spatially proximal and have similar connectivity patterns to themselves. Homophilic generative models outperform more canonical models in which neurons wire depending upon their spatial proximity either alone or in combination with the extent of their local connectivity. This homophily-based mechanism for neuronal network emergence accounts for a wide range of observations that are described, but not sufficiently explained, by traditional analyses of network topology. Using rodent and human neuronal cultures, we show that homophilic generative mechanisms can accurately recapitulate the topology of emerging cellular functional connectivity, representing an important wiring principle and determining factor of neuronal network formation in vitro.
Data availability
All data used in this study, along with documentation detailing each dataset, is openly available at https://zenodo.org/records/14544729
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Homophilic wiring principles underpin neuronal network topology in vitro10.11Zenodo 01/2022.03.09.483605.
Article and author information
Author details
Philipp J Hornauer
Andreas Hierlemann
Funding
European Research Council (694829)
- Philipp J Hornauer
- Andreas Hierlemann
- Manuel Schröter
Medical Research Council (MC-A0606-5PQ41)
- Danyal Akarca
- Alexander WE Dunn
- Duncan E Astle
James S. McDonnel Foundation
- Danyal Akarca
- Duncan E Astle
MQ: Transforming Mental Health (MQF17_24)
- Petra E Vértes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were approved by the veterinary office of the Kanton Basel-Stadt (license #2358) and carried out according to Swiss federal laws on animal welfare.
Copyright
© 2025, Akarca et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Homophilic wiring principles underpin neuronal network topology in vitro
eLife 14:e85300.
https://doi.org/10.7554/eLife.85300
