Spatio-temporal receptive field (STRF) models are frequently used to approximate the computation implemented by a sensory neuron. Typically, such STRFs are assumed to be smooth and sparse. Current state-of-the-art approaches for estimating STRFs based on empirical Bayes are often not computationally efficient in high-dimensional settings, as encountered in sensory neuroscience. Here we pursued an alternative approach and encode prior knowledge for estimation of STRFs by choosing a set of basis functions with the desired properties: natural cubic splines. Our method is computationally efficient and can be easily applied to a wide range of existing models. We compared the performance of spline-based methods to non-spline ones on simulated and experimental data, showing that spline-based methods consistently outperform the non-spli
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