Neuronal circuits overcome imbalance in excitation and inhibition by adjusting connection numbers

Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):e2018459118. doi: 10.1073/pnas.2018459118.

Abstract

The interplay between excitation and inhibition is crucial for neuronal circuitry in the brain. Inhibitory cell fractions in the neocortex and hippocampus are typically maintained at 15 to 30%, which is assumed to be important for stable dynamics. We have studied systematically the role of precisely controlled excitatory/inhibitory (E/I) cellular ratios on network activity using mice hippocampal cultures. Surprisingly, networks with varying E/I ratios maintain stable bursting dynamics. Interburst intervals remain constant for most ratios, except in the extremes of 0 to 10% and 90 to 100% inhibitory cells. Single-cell recordings and modeling suggest that networks adapt to chronic alterations of E/I compositions by balancing E/I connectivity. Gradual blockade of inhibition substantiates the agreement between the model and experiment and defines its limits. Combining measurements of population and single-cell activity with theoretical modeling, we provide a clearer picture of how E/I balance is preserved and where it fails in living neuronal networks.

Keywords: E/I balance; bursting; network dynamics; neuronal network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cells, Cultured
  • Electrophysiological Phenomena
  • Hippocampus
  • Mice
  • Models, Biological
  • Neocortex
  • Nerve Net*
  • Neuronal Plasticity*
  • Neurons / physiology*
  • Single-Cell Analysis
  • Synaptic Transmission*