Information theoretic approaches to deciphering the neural code with functional fluorescence imaging

Information theoretic metrics have proven useful in quantifying the relationship between behaviorally relevant parameters and neuronal activity with relatively few assumptions. However, these metrics are typically applied to action potential (AP) recordings and were not designed for the slow timescales and variable amplitudes typical of functional fluorescence recordings (e.g., calcium imaging). The lack of research guidelines on how to apply and interpret these metrics with fluorescence traces means the neuroscience community has yet to realize the power of information theoretic metrics. Here, we used computational methods to create mock AP traces with known amounts of information. From these, we generated fluorescence traces and examined the ability of different information metrics to recover the known information values. We provide guidelines for how to use information metrics when applying them to functional fluorescence and demonstrate their appropriate application to GCaMP6f population recordings from mouse hippocampal neurons imaged during virtual navigation.