Computational Tools for Identification and Analysis of Neuronal Population Activity

Abstract

Recently-developed technologies for monitoring activity in populations of neurons make it possible for the first time, in principle, to ask many basic questions in neuroscience. However, computational tools for analyzing newly available data need to be developed. The goal of this thesis is to contribute to this effort by focusing on two specific problems. First, we used a point-process regression framework to provide a methodology for statistical assessment of the link between neural spike synchrony and network-wide oscillations. In simulations, we showed that our method can recover ground-truth relationships, and in two types of spike train data we illustrated the kinds of results the method can produce. The approach improves on methods in the literature and may be adapted to many different experimental settings. Second, we considered the problem of source extraction in calcium imaging data, i.e., the detection of neurons within a field of view and the extraction of each neuron’s activity. The data we mainly focus on are recorded with a microendoscope, which has the unique advantage of imaging deep brain regions in freely behaving animals. These data suffer from high levels of background fluorescence, as well as the potential for overlapping neuronal signals. Based on the existing constrained nonnegative matrix factorization (CNMF) framework, we developed an efficient method to process microendoscopic data. Our method utilizes a novel algorithm to initialize the spatial shapes and temporal activity of the neurons from the raw video data independently from the strong fluctuating background. This step ensures the efficiency and accuracy of solving a nonconvex CNMF problem. Our method also models the complicated background by including its low-spatial frequency structure and the locally-low-rank feature to avoid absorbing cellular signals into the background term. We developed a tractable solution to estimate the background activity using this new model. After subtracting the approximated background, we followed the CNMF framework to demix neural signals and recover denoised and deconvolved temporal activity. We optimized several algorithms in solving the CNMF problems to get accurate results. In practice, our method outperforms all existing methods and has been adopted by many experimental labs.