Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior.

A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.