RECONSTRUCTION OF HIPPOCAMPAL CA1 PYRAMIDAL CELL ELECTROPHYSIOLOGY BYCOMPUTER-SIMULATION

1. We have developed a 16-compartment model that reproduces most of th e features of the CA1 pyramidal cell electrophysiology observed experi mentally. The model was constructed using seven active ionic conductan ces: 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 d ata obtained from these cells. We focussed the simulation on the initi al and late accommodation, the slow depolarization potential and the s pike broadening during repetitive firing, because their mechanisms are not well understood. 2. Current-clamp records were reproduced by iter ative adjustments to the ionic maximum conductances, scaling and/or '' reshaping'' of the gates' time constant within the experimental voltag e-clamp data, and shifting the position of the steady-state gate openi ng. The final properties of the ionic channels were not significantly different from the voltage-clamp experiments. 3. The resulting model r eproduces all four after-potentials that have been recorded to follow activation of the cell. The fast, medium, and slow after-hyperpolariza tion 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 rec harging of the soma by the dendrites. 4. The model also reproduces mos t of the firing features experimentally observed during injection of l ong current pulses. Model responses showed a small initial decrease in the firing frequency during a slow underlying depolarization potentia l, followed by a more significant frequency decrease. Moreover, a grad ual broadening of the action potential and loss of the fast AHP were a lso observed during the initial high-frequency firing, followed, as th e firing frequency decreased, by a gradual recovery of the spikes' ori ginal width and fast AHP amplitude increase. 5. A large reduction of t he K repolarizing current was required to reproduce the spike broadeni ng and reduction of the fast AHP experimentally observed in CA1 cells during repetitive firing responses. The incorporation of a transient C a- and voltage-dependent K current (I-CT) into the model successfully reproduced these experimental observations. In contrast, we were unabl e 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-po tential repolarization and fast AHP by a transient Ca- and voltage-dep endent K current (I-CT). 6. The two accommodation steps were induced b y a progressively enlargement of two K currents I-M (initial) and I-AH P (late). In contrast, spike broadening was induced by the reduction o f the K current I-CT. The increase of I-M and I-AHP did not significan tly increase action-potential repolarization because they are small. H owever, these small currents persisted between action potentials and w ere able to decrease the firing frequency. A reduction of I-CT decreas ed significantly the repolarization of the action potentials without s ignificantly affecting the firing frequency because I-CT is large but deactivates rapidly between consecutive spikes.