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

Krishna Choudhary, Sven Berberich, Thomas T. G. Hahn, James M. McFarland and Mayank R. Mehta ()
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Krishna Choudhary: University of California, Los Angeles
Sven Berberich: Heidelberg University
Thomas T. G. Hahn: Zentralinstitut fur Seelische Gesundheit
James M. McFarland: Brown University
Mayank R. Mehta: University of California, Los Angeles

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47617-6

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