Persistent firing is commonly reported in both cortical and subcortical neurons under a variety of behavioral conditions. Yet the mechanisms responsible for persistent activity are only partially resolved with support for both intrinsic and synaptic circuit-based mechanisms. Little also is known about physiological factors that enable epochs of persistent firing to continue beyond brief pauses and then to spontaneously terminate. In the present study, we used intracellular recordings in rat (both sexes) neocortical and hippocampal brain slices to assess the ionic mechanisms underlying persistent firing dynamics. Previously we showed that blockade of Ether-á-go-go-Related Gene (ERG) potassium channels abolished intrinsic persistent firing in the presence of low concentrations of muscarinic receptor agonists and following optogenetic activation of cholingeric axons. Here we show the slow dynamics of ERG conductance changes allows persistent firing to outlast the triggering stimulus and even initiate discharg...