Physiological models of the lateral superior olive

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones (‘shot-noise’ models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility.Author summary: Computational models help our understanding of complex biological systems, by identifying their key elements and revealing their operational principles. Close comparisons between model predictions and empirical observations ensure our confidence in a model as a building block for further applications. Most current neuronal models, however, are constructed to replicate only a small specific set of experimental data. Thus, it is usually unclear how these models can be generalized to different datasets and how they compare with each other. In this paper, seven neuronal models are examined that are designed to reproduce known physiological characteristics of auditory neurons involved in the detection of sound source location. Despite their different levels of complexity, the models generate largely similar results when their parameters are tuned with common criteria. Comparisons show that simple models are computationally more efficient and theoretically transparent, and therefore suitable for rigorous mathematical analyses and engineering applications including real-time simulations. In contrast, complex models are necessary for investigating the relationship between underlying biophysical processes and sub- and suprathreshold spiking properties, although they have a large number of unconstrained, unverified parameters. Having identified their advantages and drawbacks, these auditory neuron models may readily be used for future studies and applications.