A computer model of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells.

Despite the central position of CA3 pyramidal cells in the hippocampal circuit, the experimental investigation of their synaptic properties has been limited. Recent slice experiments from adult rats characterized AMPA and NMDA receptor unitary synaptic responses in CA3b pyramidal cells. Here, excitatory synaptic activation is modeled to infer biophysical parameters, aid analysis interpretation, explore mechanisms, and formulate predictions by contrasting simulated somatic recordings with experimental data. Reconstructed CA3b pyramidal cells from the public repository NeuroMorpho.Org were used to allow for cell-specific morphological variation. For each cell, synaptic responses were simulated for perforant pathway and associational/commissural synapses. Means and variability for peak amplitude, time-to-peak, and half-height width in these responses were compared with equivalent statistics from experimental recordings. Synaptic responses mediated by AMPA receptors are best fit with properties typical of previously characterized glutamatergic receptors where perforant path synapses have conductances twice that of associational/commissural synapses (0.9 vs. 0.5 nS) and more rapid peak times (1.0 vs. 3.3 ms). Reanalysis of passive-cell experimental traces using the model shows no evidence of a CA1-like increase of associational/commissural AMPA receptor conductance with increasing distance from the soma. Synaptic responses mediated by NMDA receptors are best fit with rapid kinetics, suggestive of NR2A subunits as expected in mature animals. Predictions were made for passive-cell current clamp recordings, combined AMPA and NMDA receptor responses, and local dendritic depolarization in response to unitary stimulations. Models of synaptic responses in active cells suggest altered axial resistivity and the presence of synaptically activated potassium channels in spines.