Bistable persistent firing reflects a neuronal state change. A, Long-lasting persistent firing triggered by a depolarizing step is abolished by the ERG antagonist ErgTx1 (50 nm; red trace). Recording from a L5 TeA neocortical PC in a slice bathed in 2 μm CCh with 0.67 μm GIRK activated ML297 added to help stabilize the membrane potential, as in the study by Cui and Strowbridge (2018). B, Diagrams of two proposed models of underlying cellular mechanism (right top and bottom). See text for details. C, Hyperpolarizing current injection for 4 s delays but does not abolish persistent activity (orange trace at top). Instantaneous firing rates from the same two responses shown below traces. D, Plot of rate-persistent firing frequency increased following stimulus offset in the same trials: p > 0.05, T = 0.045; paired t test. Mean values are indicated at the top, and N values are indicated at the bottom of each bar. E, Increasing the duration of the depolarizing step stimulus does not affect persistent firing frequency. Example responses evoked by 500 and 2 s depolarizing steps recorded from the same neuron and at the same membrane potential. F, Summary plot of average persistent firing frequency evoked by 500 ms and 2 s depolarizing steps in 6 PCs: p > 0.05; paired t test using same cell comparisons. Experiments illustrated in C–F were conducted using 2 μm CCh without ML297.