Simulation of Ca+2 Persistent Inward Currents in Spinal Motoneurons: Mode of Activation and Integration of Synaptic Inputs

The goal of this study was to investigate the nature of activation of the dendritic calcium persistent inward current (Ca2+ PIC) and its contribution to the enhancement and summation of synaptic inputs in spinal motoneurones. A compartmental cable model of a catα-motoneurone was developed comprising the realistic dendritic distribution of Ia-afferent synapses and low-voltage-activated L-type calcium (Cav1.3) channels distributed over the dendrites in a manner that was previously shown to match a wide set of experimental measurements. The level of synaptic activation was systematically increased and the resulting firing rate, somatic and dendritic membrane potentials, dendritic Cav1.3 channel conductance, and dendritic Ca2+ PIC were measured. Our simulation results suggest that during cell firing the dendritic Ca2+ PIC is not activated in an all-or-none manner. Instead, it is initially activated in a graded manner with increasing synaptic input until it reaches its full activation level, after which additional increases in synaptic input result in minimal changes in the Ca2+ PIC (PIC saturated). The range of graded activation of Ca2+ PICoccurs when the cell is recruited and causes a steep increase in the firing frequency as the synaptic current is increased, coinciding with the secondary range of the synaptic frequency–current (F–I)relationship.Once theCa2+ PICissaturated the slope of theF–I relationship is reduced, corresponding to the tertiary range of firing.When the post-spike after-hyperpolarization (AHP) is blocked, either directly by blocking the calcium-activated potassium channels, or indirectly by blocking the sodium spikes, the PIC is activated in an all-or-none manner with increasing synaptic input. Thus, the AHP serves to limit the depolarization of the cell during firing and enables graded, rather than all-or-none, activation of the Ca2+ PIC. The graded activation of the Ca2+ PIC with increasing synaptic input results in a graded (linear) enhancement and linear summation of synaptic inputs. In contrast, the saturated Ca2+ PIC enhances synaptic inputs by a constant amount (constant current), and leads to less-than linear summation of multiple synaptic inputs. These model predictions improve our understanding of the mode of activation of the dendritic Ca2+ PIC and its role in the enhancement and integration of synaptic inputs