Kv7 and Kir6 Channels Shape the Slow AHP in Mouse Dentate Gyrus Granule Cells and Control Burst-like Firing Behavior. (15th July 2021)

• Record Type: Journal Article
• Authors: Laker, Debora; Tolle, Frederik; Stegen, Michael; Heerdegen, Marco; Köhling, Rüdiger; Kirschstein, Timo; Wolfart, Jakob
• Is Part Of: Neuroscience. Volume 467(2021)
• Page Start: 56
• Page End: 72
• Publication Date: 2021-07-15
• Subjects: ACSF artificial cerebrospinal fluid -- APs action potentials -- DG dentate gyrus -- DGCs dentate granule cells -- fEPSP field excitatory postsynaptic potential -- LTP long-term potentiation -- NCS neuronal calcium sensor -- sAHP slow afterhyperpolarizing potential -- SFA spike-frequency adaptation; slow afterhyperpolarization -- ATP-sensitive channels -- KCNQ channels -- rheobase -- LTP; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.05.025
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: 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. Abstract: 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 (IsAHP ) amplitude compared to spike-frequency adapting cells (16/113 = 14%). The IsAHP was mediated by Kv 7 and Kir 6 channels by pharmacological inhibition using XE991 and tolbutamide, although heterogeneously among DGCs. The percent inhibition of IsAHP 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.