Efficient estimation of neural tuning during naturalistic behavior

Recent technological advances in systems neuroscience have led to a shift away from using simple tasks with low-dimensional, well-controlled stimuli towards trying to understand neural activity during naturalistic behavior. However, with the increase in number and complexity of task-relevant features, standard analyses such as estimating tuning functions become challenging. Here, we use a Poisson generalized additive model (P-GAM) with spline nonlinearities and an exponential link function to map a large number of task variables (input stimuli, behavioral outputs, and activity of other neurons, modeled as discrete events or continuous variables) into spike counts. We develop efficient procedures for parameter learning by optimizing a generalized cross-validation score and infer marginal confidence bounds for the contribution of each feature to neural responses. This allows us to robustly identify a minimal set of task features that each neuron is responsive to, circumventing computationally demanding model comparison. We show that our estimation procedure outperforms traditional regularized GLMs in terms of both fit quality and computing time. When applied to neural recordings from monkeys performing a virtual reality spatial navigation task, P-GAM reveals mixed selectivity and preferential coupling between neurons with similar tuning.