Dendritic interaction of timescales in afterdepolarization potentials and nonmonotonic spike-adding

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-compartment Hodgkin-Huxley type model of cerebellar stellate cells, 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 input resulted in nonmonotonic spike-adding in a manner dependent on dendritic Ca²⁺ influx and Ca²⁺ activated K⁺ currents, which was found to arise from 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 ADPs and spike-adding regulation highlights the role of currents with slow timescales in ADPs, stimulus evoked transient bursting and neuronal excitability with implications for Ca²⁺ dependent synaptic plasticity and neuromodulation.