Modeling functional cell types in spike train data

Abstract

A major goal of computational neuroscience is to build accurate models of the activity of neurons that can be used to interpret their function in circuits. Here, we explore using functional cell types to refine single-cell models by grouping them into functionally relevant classes. Formally, we define a hierarchical generative model for cell types, single-cell parameters, and neural responses, and then derive an expectation-maximization algorithm with variational inference that maximizes the likelihood of the neural recordings. We apply this "simultaneous" method to estimate cell types and fit single-cell models from simulated data, and find that it accurately recovers the ground truth parameters. We then apply our approach to in vitro neural recordings from neurons in mouse primary visual cortex, and find that it yields improved prediction of single-cell activity. We demonstrate that the discovered cell-type clusters are well separated and generalizable, and thus amenable to interpretation. We then compare discovered cluster memberships with locational, morphological, and transcriptomic data. Our findings reveal the potential to improve models of neural responses by explicitly allowing for shared functional properties across neurons. Author SummaryComputational neuroscience has its roots in fitting and interpreting predictive models of the activity of individual neurons. In recent years, more attention has focused on models of how ensembles of neurons work together to perform computations. However, fitting these more complex models to data is challenging, limiting our ability to use them to understand real neural systems. One idea that has improved our understanding of populations of neurons is cell types, where neurons of the same type have similar properties. While the idea of cell types is old, recent work has focused on functional cell types, where the properties of interest are derived from fitted predictive models of the activity of single neurons. In this work, we develop a method that simultaneously fits a predictive model of each neurons activity and groups neurons into functional cell types. Compared to existing techniques, this method produces more accurate models of single-cell neural activity and better groupings of neurons into types. This method can thus contribute in using cell types to better understanding the components of neural systems based on our increasingly rich observations of their functional responses.