Fig 1. The CAN current supports persistent firing in the single cell model.

(A) Response of an in vitro hippocampal CA3 pyramidal cell in the normal ACSF. The brief current injection did not induce persistent firing. Ionotropic synaptic blockers, 20 μM CNQX, 50 μM D,L-APV and 100 μM PTX, were present in all in vitro recordings to block AMPA/kainite receptors, NMDA receptors and GABA_A receptors, respectively. (B) Response of the same cell in carbachol (10 μM). Long-lasting (≥ 30 s) persistent firing is observed after the same brief stimulation. (C) Self-terminating persistent firing (< 30 s) was observed in the same condition as in B in some cells. (D) Response of the single pyramidal cell model to a brief current injection without the CAN current. No persistent firing was seen. (E) Long-lasting persistent firing observed in the single pyramidal cell model with 100% CAN current. (F) Self-terminating persistent firing observed in the single pyramidal cell model with 90% CAN current. (G-I) Further reduction of the CAN current caused self-terminating persistent firing with shorter durations (G and H) and an after-depolarization without spikes (I). In all figures, (i) Membrane potential, (ii) Frequency of firing, (iii) Intracellular calcium concentration, (iv) CAN current conductance, and (v) Current injection.