A new bursting model of CA3 pyramidal cell physiology suggests multiple locations for spike initiation.

We introduce a novel computational model of hippocampal pyramidal cells physiology based on an up-to-date, detailed description of passive and active biophysical properties and real dendritic morphology. This model constitutes a modification of a previous (1995) model which included complex calcium dynamics and Na(+), K(+), and Ca(2+) currents. Changes reflect recently acquired experimental knowledge regarding the types and spatial distributions of these currents. The updated model responds to simulated somatic current clamp stimulation with a train of spikes (burst). The shape of the burst reproduces the characteristic behavior observed experimentally, similarly to the previous model. However, an analysis of dendritic membrane voltage distribution during the burst shows that the mechanisms underlying this somatic behavior are dramatically different in the two models. In the previous model, all spikes were generated in the soma and backpropagated in the dendrites. In the updated model, in contrast, only the first spike is initiated somatically. The second somatic spike is preceded by a dendritic spike (triggered by the first spike backpropagation), which propagates both backward and forward, reaching the soma just before the rise of the second somatic spike. The third and fourth spikes are similarly caused by a complex spatio-temporal interplay between somatic and dendritic depolarization. These results suggest that the distribution of ionic currents recently characterized in hippocampal pyramidal cells can support both somatic and dendritic spike initiation. In addition, these simulations demonstrate that models with considerably different distributions of active conductances can reproduce the same experimental bursting behavior with distinct biophysical mechanisms.