Parameter Optimization Using Covariance Matrix Adaptation-Evolutionary Strategy (CMA-ES), an Approach to Investigate Differences in Channel Properties Between Neuron Subtypes.

Computational models in neuroscience can be used to predict causal relationships between biological mechanisms in neurons and networks, such as the effect of blocking an ion channel or synaptic connection on neuron activity. Since developing a biophysically realistic, single neuron model is exceedingly difficult, software has been developed for automatically adjusting parameters of computational neuronal models. The ideal optimization software should work with commonly used neural simulation software; thus, we present software which works with models specified in declarative format for the MOOSE simulator. Experimental data can be specified using one of two different file formats. The fitness function is customizable as a weighted combination of feature differences. The optimization itself uses the covariance matrix adaptation-evolutionary strategy, because it is robust in the face of local fluctuations of the fitness function, and deals well with a high-dimensional and discontinuous fitness landscape. We demonstrate the versatility of the software by creating several model examples of each of four types of neurons (two subtypes of spiny projection neurons and two subtypes of globus pallidus neurons) by tuning to current clamp data. Optimizations reached convergence within 1,600-4,000model evaluations (200-500 generations x population size of 8). Analysis of the parameters of the best fitting models revealed differences between neuron subtypes, which are consistent with prior experimental results. Overall our results suggest that this easy-to-use, automatic approach for finding neuron channel parameters may be applied to current clamp recordings fromneurons exhibiting different biochemicalmarkers to help characterize ionic differences between other neuron subtypes.