Emergence of assortative mixing between clusters of cultured neurons

PLoS Comput Biol. 2014 Sep 4;10(9):e1003796. doi: 10.1371/journal.pcbi.1003796. eCollection 2014 Sep.


The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a 'connectivity backbone' in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Embryo, Mammalian
  • Models, Neurological*
  • Nerve Net
  • Neurons / cytology*
  • Neurons / physiology*
  • Rats
  • Rats, Sprague-Dawley

Grant support

Research was supported by the Ministerio de Ciencia e Innovaci\'on (Spain, www.idi.mineco.gob.es) under projects FIS2010-21924-C02-02, FIS2011-28820-C02-01, FIS2012-38266-C02-01, and FIS2010-09832-E. We also acknowledge the Generalitat de Catalunya (www10.gencat.cat/agaur_web) under projects 2009-SGR-00014 and 2009-SGR-838, and the EU FET (MULTIPLEX 317532). A.A. also acknowledges partial financial support from the ICREA Academia and the James S.\ McDonnell Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.