Inference of Multiplicative Factors Underlying Neural Variability in Calcium Imaging Data.

Understanding brain function requires disentangling the high-dimensional activity of populations of neurons. Calcium imaging is an increasingly popular technique for monitoring such neural activity, but computational tools for interpreting extracted calcium signals are lacking. While there has been a substantial development of factor analysis-type methods for neural spike train analysis, similar methods targeted at calcium imaging data are only beginning to emerge. Here we develop a flexible modeling framework that identifies low-dimensional latent factors in calcium imaging data with distinct additive and multiplicative modulatory effects. Our model includes spike-and-slab sparse priors that regularize additive factor activity and gaussian process priors that constrain multiplicative effects to vary only gradually, allowing for the identification of smooth and interpretable changes in multiplicative gain. These factors are estimated from the data using a variational expectation-maximization algorithm that requires a differentiable reparameterization of both continuous and discrete latent variables. After demonstrating our method on simulated data, we apply it to experimental data from the zebrafish optic tectum, uncovering low-dimensional fluctuations in multiplicative excitability that govern trial-to-trial variation in evoked responses.