RECONSTRUCTION OF HIPPOCAMPAL CA1 PYRAMIDAL CELL ELECTROPHYSIOLOGY BY COMPUTER-SIMULATION

1. We have developed a 16-compartment model that reproduces most of the features of the CA1 pyramidal cell electrophysiology observed experimentally. The model was constructed using seven active ionic conductances: g(Na), g(Ca), g(DR), g(CT), g(A), g(M), and g(AHP) whose kinetics have been inferred, in most cases, from the available voltage-clamp data obtained from these cells. We focussed the simulation on the initial and late accommodation, the slow depolarization potential and the spike broadening during repetitive firing, because their mechanisms are not well understood. 2. Current-clamp records were reproduced by iterative adjustments to the ionic maximum conductances, scaling and/or ''reshaping'' of the gates' time constant within the experimental voltage-clamp data, and shifting the position of the steady-state gate opening. The final properties of the ionic channels were not significantly different from the voltage-clamp experiments. 3. The resulting model reproduces all four after-potentials that have been recorded to follow activation of the cell. The fast, medium, and slow after-hyperpolarization potentials (AHPs) were, respectively, generated by I-CT, I-M, and I-AHP. Furthermore, the model suggests that the mechanisms underlying the depolarization after potential (DAP) is mostly due to passive recharging of the soma by the dendrites. 4. The model also reproduces most of the firing features experimentally observed during injection of long current pulses. Model responses showed a small initial decrease in the firing frequency during a slow underlying depolarization potential, followed by a more significant frequency decrease. Moreover, a gradual broadening of the action potential and loss of the fast AHP were also observed during the initial high-frequency firing, followed, as the firing frequency decreased, by a gradual recovery of the spikes' original width and fast AHP amplitude increase. 5. A large reduction of the K repolarizing current was required to reproduce the spike broadening and reduction of the fast AHP experimentally observed in CA1 cells during repetitive firing responses. The incorporation of a transient Ca- and voltage-dependent K current (I-CT) into the model successfully reproduced these experimental observations. In contrast, we were unable to reproduce this phenomenon when a large persistent Ca- and voltage-dependent K current (generally named I-C) was included in the model. These results suggest that there is a strong contribution to action-potential repolarization and fast AHP by a transient Ca- and voltage-dependent K current (I-CT). 6. The two accommodation steps were induced by a progressively enlargement of two K currents I-M (initial) and I-AHP (late). In contrast, spike broadening was induced by the reduction of the K current I-CT. The increase of I-M and I-AHP did not significantly increase action-potential repolarization because they are small. However, these small currents persisted between action potentials and were able to decrease the firing frequency. A reduction of I-CT decreased significantly the repolarization of the action potentials without significantly affecting the firing frequency because I-CT is large but deactivates rapidly between consecutive spikes.