Online Supplement : About the Model

In Section 1 of this supplement, we describe the process of constructing the pyramidal cell model. In Section 2, we show results of the validation studies used to calibrate the model based on data from published in vitro physiological studies. The parameters of the model are described in detail in Section 3. 1 Building the Model Our goal was to construct and validate a state-of-the-art compartmental model of a CA1 pyramidal cell. Construction of the model was an immense project, as it involved adjusting the internal parameters of 17 types of ion channels, most of them distributed nonuniformly along the soma-dendritic axis, and 4 types of synaptic conductances. Constraints on the model arose from two main sources, including (1) data from studies primarily concerned with individual channel properties, including activation and inactivation curves, time constants, location-dependent channel densities, etc., and (2) data from studies primarily concerned with dendritic physiology and synaptic integration, including responses to current, voltage, and/or synaptic stimuli. In some cases, NEURON channel models developed by others were used with little or no modification, as detailed in Section 3. In spite of the complexity of the model as a whole, we were able through a lengthy manual iteration process to achieve good fits to a variety of experimental data, covering a broader range of phenomena than is handled by other pyramidal cell models that we know of. While we do not claim that the model is a perfect simulacrum of the real cell, its ability

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