Approaches to Parameter Estimation from Model Neurons and Biological Neurons

Model optimization in neuroscience has focused on inferring intracellular parameters from time series observations of the membrane voltage and calcium concentrations. These parameters constitute the fingerprints of ion channel subtypes and may identify ion channel mutations from observed changes in electrical activity. A central question in neuroscience is whether computational methods may obtain ion channel parameters with sufficient consistency and accuracy to provide new information on the underlying biology. Finding single-valued solutions in particular, remains an outstanding theoretical challenge. This note reviews recent progress in the field. It first covers well-posed problems and describes the conditions that the model and data need to meet to warrant the recovery of all the original parameters-even in the presence of noise. The main challenge is model error, which reflects our lack of knowledge of exact equations. We report on strategies that have been partially successful at inferring the parameters of rodent and songbird neurons, when model error is sufficiently small for accurate predictions to be made irrespective of stimulation.