Nature Communications (May 2024)

Spontaneous persistent activity and inactivity in vivo reveals differential cortico-entorhinal functional connectivity

  • Krishna Choudhary,
  • Sven Berberich,
  • Thomas T. G. Hahn,
  • James M. McFarland,
  • Mayank R. Mehta

DOI
https://doi.org/10.1038/s41467-024-47617-6
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 15

Abstract

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Abstract Understanding the functional connectivity between brain regions and its emergent dynamics is a central challenge. Here we present a theory-experiment hybrid approach involving iteration between a minimal computational model and in vivo electrophysiological measurements. Our model not only predicted spontaneous persistent activity (SPA) during Up-Down-State oscillations, but also inactivity (SPI), which has never been reported. These were confirmed in vivo in the membrane potential of neurons, especially from layer 3 of the medial and lateral entorhinal cortices. The data was then used to constrain two free parameters, yielding a unique, experimentally determined model for each neuron. Analytic and computational analysis of the model generated a dozen quantitative predictions about network dynamics, which were all confirmed in vivo to high accuracy. Our technique predicted functional connectivity; e. g. the recurrent excitation is stronger in the medial than lateral entorhinal cortex. This too was confirmed with connectomics data. This technique uncovers how differential cortico-entorhinal dialogue generates SPA and SPI, which could form an energetically efficient working-memory substrate and influence the consolidation of memories during sleep. More broadly, our procedure can reveal the functional connectivity of large networks and a theory of their emergent dynamics.