Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell

The rules of synaptic integration in pyramidal cells remain obscure, in part due to conflicting interpretations of existing experimental data. To clarify issues, we developed a CA1 pyramidal cell model calibrated with a broad spectrum of in vitro data. Using simultaneous dendritic and somatic recordings and combining results for two different response measures (peak versus mean EPSP), two different stimulus formats (single shock versus 50 Hz trains), and two different spatial integration conditions (within versus between-branch summation), we found that the cell's subthreshold responses to paired inputs are best described as a sum of nonlinear subunit responses, where the subunits correspond to different dendritic branches. In addition to suggesting a new type of experiment and providing testable predictions, our model shows how conclusions regarding synaptic arithmetic can be influenced by an array of seemingly innocuous experimental design choices.