Spontaneous coordinated activity in cultured networks: Analysis of multiple ignition sites, primary circuits, burst phase delay distributions and functional structures

TL;DR

This study investigates spontaneous neural activity in cultured cortical networks, identifying leader neurons, analyzing burst dynamics, and revealing how inhibitory blocking affects network timing and information flow.

Contribution

It introduces methods to analyze ignition sites, primary circuits, and burst delay distributions, providing new insights into the internal dynamics of spontaneous neural activity.

Findings

Leader neurons form primary circuits initiating bursts

Blocking inhibition shortens delay times and reduces variance

Mutual information correlates with physical distance between neurons

Abstract

All higher order central nervous systems exhibit spontaneous neural activity, though the purpose and mechanistic origin of such activity remains poorly understood. We explore the ignition and spread of collective spontaneous electrophysiological burst activity in networks of cultured cortical neurons growing on microelectrode arrays using information theory and first-spike-in-burst analysis methods. We show the presence of burst leader neurons, which form a mono-synaptically connected primary circuit, and initiate a majority of network bursts. Leader/follower firing delay times form temporally stable positively skewed distributions. Blocking inhibitory synapses usually results in shorter delay times with reduced variance. These distributions are generalized characterizations of internal network dynamics and provide estimates of pair-wise synaptic distances. We show that mutual information between neural nodes is a function of distance, which is maintained under disinhibition. The resulting analysis produces specific quantitative constraints and insights into the activation patterns of collective neuronal activity in self-organized cortical networks, which may prove useful for models emulating spontaneously active systems.