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

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.