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  • Open Access

Collective Dynamics of Frustrated Biological Neuron Networks

Guanyu Li1,*, Ryan LeFebre2,*, Alia Starman3, Patrick Chappell3,†, Andrew Mugler2,‡, and Bo Sun1,§

  • *These authors contributed equally to this work.
  • †Contact author: chappelp@oregonstate.edu
  • ‡Contact author: andrew.mugler@pitt.edu
  • §Contact author: sunb@oregonstate.edu
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PRX Life 3, 033002 – Published 2 July, 2025

DOI: https://doi.org/10.1103/1258-cl48

Abstract

To maintain normal functionality, it is necessary for a multicellular organism to generate robust responses to external temporal signals. However, the underlying mechanisms to coordinate the collective dynamics of cells remain poorly understood. Here, we study the calcium activity of biological neuron networks excited by periodic ATP stimuli. We use micropatterning to control the cells' physical connectivity. We find that whereas isolated cells become more synchronized in their calcium activity at long driving periods, connected cells become less synchronized, despite expressing more gap junctions which enable calcium exchange. To understand this result, we use a mathematical model in which a bifurcation analysis has previously shown coupling-induced desynchronization in an oscillatory network. Using parameters close to this bifurcation but in the excitable regime, we find that this desynchronization persists and can explain the experimental observations. The model further predicts that co-culturing with gap-junction-deficient cells should restore synchronization, which experiments confirm. Combining quantitative experiments, the physical and biological manipulation of cells, and mathematical modeling, our results suggest that cell-to-cell connectivity significantly affects how populations encode an external temporal signal as it slows down: Sparse networks synchronize due to longer entrainment, whereas highly connected networks can desynchronize due to dynamic frustration.

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PRX Life 3, 033002– Published 2 July, 2025
  • Received 18 November 2024
  • Accepted 3 June 2025
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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