Kv7 and Kir6 Channels Shape the Slow AHP in Mouse Dentate Gyrus Granule Cells and Control Burst-like Firing Behavior.

• DGCs express sAHP-mediating currents associated with a burst-like phenotype. • The sAHP-mediating current is carried by at least Kv7 and Kir6 channels. • Perforant path-dentate gyrus LTP is amplified by blocking sAHP-mediating currents. The slow afterhyperpolarizing potential (sAHP) can silence a neuron for hundreds of milliseconds. Thereby, the sAHP determines the discharge behavior of many types of neurons. In dentate granule cells (DGCs), serving as a filter into the hippocampal network, mostly tonic or adapting discharge properties have been described. As under standard whole-cell recording conditions the sAHP is inhibited, we reevaluated the intrinsic functional phenotype of DGCs and the conductances underlying the sAHP, using gramicidine-perforated patch-clamp technique. We found that in 97/113 (86%) of the DGCs, a burst of action potentials (APs) to excitation ended by a large sAHP, despite continued depolarization. This result suggests that burst-like firing is the default functional phenotype of DGCs and that sAHPs are important for it. Indeed, burst-like firing DGCs showed a significantly higher sAHP-current (I sAHP) amplitude compared to spike-frequency adapting cells (16/113 = 14%). The I sAHP was mediated by K v 7 and K ir 6 channels by pharmacological inhibition using XE991 and tolbutamide, although heterogeneously among DGCs. The percent inhibition of I sAHP by these compounds also correlated with the AP number and AP burst length. Application of 100 µM nickel after XE991 and tolbutamide detected a third conductance contributing to burst-like firing and the sAHP, most likely mediated by T-type calcium channels. Lastly, medial perforant path-dentate gyrus long-term potentiation was amplified by XE991 and tolbutamide. In conclusion, the sAHP shapes intrinsic burst-like firing which, under physiological circumstances, could be controlled via cholinergic afferents and ATP metabolism. [ABSTRACT FROM AUTHOR]