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All higher order central nervous systems exhibit spontaneous neural activity,though the purpose and mechanistic origin of such activity remains poorlyunderstood. We explore the ignition and spread of collective spontaneouselectrophysiological burst activity in networks of cultured cortical neuronsgrowing on microelectrode arrays using information theory andfirst-spike-in-burst analysis methods. We show the presence of burst leaderneurons, which form a mono-synaptically connected primary circuit, and initiatea majority of network bursts. Leader/follower firing delay times formtemporally stable positively skewed distributions. Blocking inhibitory synapsesusually results in shorter delay times with reduced variance. Thesedistributions are generalized characterizations of internal network dynamicsand provide estimates of pair-wise synaptic distances. We show that mutualinformation between neural nodes is a function of distance, which is maintainedunder disinhibition. The resulting analysis produces specific quantitativeconstraints and insights into the activation patterns of collective neuronalactivity in self-organized cortical networks, which may prove useful for modelsemulating spontaneously active systems.

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