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bioRxiv · 10.1101/2025.09.26.678799

Dendritic Interaction of Timescales in Afterdepolarization Potentials and Nonmonotonic Spike--adding

Koch, N. A.·Zhao, Y.·Khadra, A.
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Abstract

Depolarizations that occur after action potentials, known as afterdepolarization potentials or ADPs, are important for neuronal excitability and stimulus evoked transient bursting. Slow inward and fast outward currents underlie the generation of such ADPs with modulation of ADP amplitudes occurring as a result of neuronal morphology. However, the relative contribution and role of these slow inward and fast outward currents in ADP generation is poorly understood in the context of somatic and dendritic localization as well as with varied dendritic properties. Using a two compartmental Hodgkin-Huxley type model, the role of somatic and dendritic compartmentalization of ADP associated currents is investigated, revealing that dendritic (rather than somatic) slow inward and fast outward currents are the main contributors to ADP and spike-adding during both brief step current and AMPA current input. Additionally, dendritic size and passive properties of the dendrites were found to be key modulators of ADP amplitude. However, increasing magnitudes of NMDA current conductance resulted in nonmonotonic spike-adding in a manner dependent on dendritic Ca2+ influx and Ca2+ activated K+ currents, which was found to be the result of tight regulation of stimulus evoked transient bursting through positive feedback on action potential generation by dendritic Ca2+ and subsequent negative feedback through Ca2+ activated K+ currents. This novel mechanism of ADP and spike-adding regulation highlights the role of currents with slow timescales in ADPs, stimulus evoked bursting and neuronal excitability with implications for Ca2+ dependent synaptic plasticity and neuromodulation.

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Koch, N. A., Zhao, Y., Khadra, A.. 2025-09-28. Dendritic Interaction of Timescales in Afterdepolarization Potentials and Nonmonotonic Spike--adding. https://doi.org/10.1101/2025.09.26.678799

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