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bioRxiv · 10.1101/2021.05.07.443074

Inhibition-Dominated Rich-Club Shapes Dynamics in Cortical Microcircuits of Awake Behaving Mice

Hafizi, H.·Nigam, S.·Barnathan, J.·Stevenson, I.·Masmanidis, S. C.·Newman, E. L.·Sporns, O.·Beggs, J.
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Abstract

Functional networks of cortical neurons contain highly interconnected hubs, forming a rich-club structure. However, the cell type composition within this distinct subnetwork and how it influences large-scale network dynamics is unclear. Using spontaneous activity recorded from hundreds of cortical neurons in orbitofrontal cortex of awake behaving mice and from organotypic cultures, we show that the rich-club is disproportionately composed of inhibitory neurons, and that inhibitory neurons within the rich-club are significantly more synchronous than other neurons. At the population level, neurons in the rich-club exert higher than expected Granger causal influence on overall population activity at a broad range of frequencies compared to other neurons. Finally, neuronal avalanche duration is significantly correlated with the fraction of rich neurons that participate in the avalanche. Together, these results suggest an unexpected role of a highly connected, inhibition-rich subnetwork in driving and sustaining activity in local cortical networks. SIGNIFICANCE STATEMENTIt is widely believed that the relative abundance of excitatory and inhibitory neurons in cortical circuits is roughly 4:1. This relative abundance has been widely used to construct numerous cortical network models. Here we show that contrary to this notion, a sub-network of highly connected hub neurons (rich-club) consists of a higher abundance of inhibitory neurons compared to that found in the entire network or the non-rich subnetwork. Inhibitory hub neurons contribute to higher synchrony within the rich club compared to the rest of the network. Strikingly, higher activation of the inhibition-dominated rich club strongly correlates with longer avalanches in cortical circuits. Our findings reveal how network topology combined with cell-type specificity orchestrates population wide activity in cortical microcircuits.

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Hafizi, H., Nigam, S., Barnathan, J., Stevenson, I., Masmanidis, S. C., Newman, E. L., Sporns, O., Beggs, J.. 2021-05-09. Inhibition-Dominated Rich-Club Shapes Dynamics in Cortical Microcircuits of Awake Behaving Mice. https://doi.org/10.1101/2021.05.07.443074

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