%0 Journal Article %A Niccolò Calcini %A Angelica da Silva Lantyer %A Fleur Zeldenrust %A Tansu Celikel %T Nonlinear super-resolution signal processing for subcellular analysis of calcium dynamics %D 2022 %R 10.1101/2022.01.29.478290 %J bioRxiv %P 2022.01.29.478290 %X Optical (fluorescence) imaging of ionic dynamics has revolutionized neuroscience as it allows the study of neural activity across spatially identified populations. Quantification of fluorescence signals is commonly performed using ratiometric measures, like the ΔF/F. Although these measures are robust and easy to implement, they do not take advantage of the temporal information available in time-varying signals. Moreover, since a baseline (reference) period needs to be selected, their application is often limited to the quantification of stimulus-evoked activity. Here, we present a new approach, called ARES, based on the quantification of residuals after linear autoregression. We demonstrate the utility of ARES to quantify the functional dynamics of stimulus representation in cortical networks and show that it improves the spatial and temporal resolution with respect to ΔF/F. We further show that ARES can be used to study subcellular calcium dynamics and exemplify its utility to describe the spatiotemporal dynamics of calcium signal localization in compartmental network recordings. ARES offers a novel method for quantitative analysis of optical imaging dataAuthor summary Two-photon calcium imaging is a powerful and non-invasive method to measure and visualize the activity of neural populations in single cell and subcellular resolution. However, the slow dynamics of both the calcium signal itself and its indicators make it difficult to relate the timing and origin of the neural activity to the calcium signal. The most commonly used analysis method, ΔF/F, uses a reference baseline to quantify signal ratiometrically. This results in several limitations, especially in accounting for the time varying fluctuations in fluorescence values. Here we present a new method for the analysis of calcium signals, called ARES, in which a sliding window is used to predict the future values of the signal and deviations from this prediction are recorded as the signal. This has the advantage that shifts in baseline do not affect the processing, and that the method has an improved spatial and temporal resolution with respect to ΔF/F.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2022/01/29/2022.01.29.478290.full.pdf