Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type

Abstract

To improve bench-to-bedside translation, it is integral that knowledge flow bidirectionally from - animal models to humans, and vice versa. This will be facilitated by the application of common analytical frameworks, as well as open software and data sharing practices. To these ends, we share a new pipeline (and test dataset) for the preprocessing of wide-field optical fluorescence imaging data - an emerging mode applicable in animal models - as well as results from a functional connectivity and graph theory analysis of these data that is inspired by recent work in the human neuroimaging field. The approach is demonstrated using a dataset comprised of two test-cases: (1) data from animals imaged during awake and anesthetized conditions with excitatory neurons labeled, and (2) data from awake animals with different genetically encoded fluorescent labels that target either excitatory neurons or inhibitory interneuron subtypes. Both seed-based connectivity and graph theory measures (global efficiency, transitivity, modularity, and characteristic path-length) are shown to be useful in quantifying differences between consciousness states and cell populations. The graph theory measures are shown to be capable of characterizing the dependence on canonical network and frequency band (infra-slow versus delta). Both consciousness state and cell population show widespread effects on canonical network connectivity with variable frequency band dependence. Effects of anesthesia are also revealed across graph theory measures (particularly in the delta band). Differences between excitatory neurons and inhibitory interneurons are observed, with somatostatin expressing inhibitory interneurons emerge as notably dissimilar from parvalbumin and vasoactive polypeptide expressing cells. We recommend this pipeline as a step in harmonization between preclinical and human research enabling comparison of results across both scales and species.