Learning Structure in Time Series for Neuroscience and Beyond

Advances in neuroscience are producing data at an astounding rate - data which are fiendishly complex both to process and to interpret. Biological neural networks are high-dimensional, nonlinear, noisy, heterogeneous, and in nearly every way defy the simplifying assumptions of standard statistical methods. In this dissertation we address a number of issues with understanding the structure of neural populations, from the abstract level of how to uncover structure in generic time series, to the practical matter of finding relevant biological structure in state-of-the-art experimental techniques. To learn the structure of generic time series, we develop a new statistical model, which we dub the probabilistic deterministic infinite automata (PDIA), which uses tools from nonparametric Bayesian inference to learn a very general class of sequence models. We show that the models learned by the PDIA often offer better predictive performance and faster inference than Hidden Markov Models, while being significantly more compact than models that simply memorize contexts. For large populations of neurons, models like the PDIA become unwieldy, and we instead investigate ways to robustly reduce the dimensionality of the data. In particular, we adapt the generalized linear model (GLM) framework for regres- sion to the case of matrix completion, which we call the low-dimensional GLM. We show that subspaces and dynamics of neural activity can be accurately recovered from model data, and with only minimal assumptions about the structure of the dynamics can still lead to good predictive performance on real data. Finally, to bridge the gap between recording technology and analysis, particularly as recordings from ever-larger populations of neurons becomes the norm, automated methods for extracting activity from raw recordings become a necessity. We present a number of methods for automatically segmenting biological units from optical imaging data, with applications to light sheet recording of genetically encoded calcium indicator fluorescence in the larval zebrafish, and optical electrophysiology using genetically encoded voltage indicators in culture. Together, these methods are a powerful set of tools for addressing the diverse challenges of modern neuroscience.