Kv7 and Kir6 Channels Shape the Slow AHP in Mouse Dentate Gyrus Granule Cells and Control Burst-like Firing Behavior
| Autor: | Frederik Tolle, Jakob Wolfart, Michael Stegen, Rüdiger Köhling, Marco Heerdegen, Timo Kirschstein, Debora Laker |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Voltage-dependent calcium channel Chemistry General Neuroscience Dentate gyrus Long-term potentiation Depolarization Hippocampal formation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Rheobase Slow afterhyperpolarization medicine Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 467:56-72 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2021.05.025 |
| Popis: | 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 Kv7 and Kir6 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. |
| Databáze: | OpenAIRE |
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