Fairhall
Adrienne
Fairhall
Adrienne
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ArticleTracking calcium dynamics from individual neurons in behaving animals(Public Library of Science, 2021-10-08) Lagache, Thibault ; Hanson, Alison ; Pérez-Ortega, Jesús E. ; Fairhall, Adrienne ; Yuste, RafaelMeasuring the activity of neuronal populations with calcium imaging can capture emergent functional properties of neuronal circuits with single cell resolution. However, the motion of freely behaving animals, together with the intermittent detectability of calcium sensors, can hinder automatic monitoring of neuronal activity and their subsequent functional characterization. We report the development and open-source implementation of a multi-step cellular tracking algorithm (Elastic Motion Correction and Concatenation or EMC2) that compensates for the intermittent disappearance of moving neurons by integrating local deformation information from detectable neurons. We demonstrate the accuracy and versatility of our algorithm using calcium imaging data from two-photon volumetric microscopy in visual cortex of awake mice, and from confocal microscopy in behaving Hydra, which experiences major body deformation during its contractions. We quantify the performance of our algorithm using ground truth manual tracking of neurons, along with synthetic time-lapse sequences, covering a wide range of particle motions and detectability parameters. As a demonstration of the utility of the algorithm, we monitor for several days calcium activity of the same neurons in layer 2/3 of mouse visual cortex in vivo, finding significant turnover within the active neurons across days, with only few neurons that remained active across days. Also, combining automatic tracking of single neuron activity with statistical clustering, we characterize and map neuronal ensembles in behaving Hydra, finding three major non-overlapping ensembles of neurons (CB, RP1 and RP2) whose activity correlates with contractions and elongations. Our results show that the EMC2 algorithm can be used as a robust and versatile platform for neuronal tracking in behaving animals.
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ArticleA complete biomechanical model of Hydra contractile behaviors, from neural drive to muscle to movement(National Academy of Sciences, 2023-03-14) Wang, Hengji ; Swore, Joshua ; Sharma, Shashank ; Szymanski, John R. ; Yuste, Rafael ; Daniel, Thomas L. ; Regnier, Michael ; Bosma, Martha M. ; Fairhall, Adrienne L.How does neural activity drive muscles to produce behavior? The recent development of genetic lines inthat allow complete calcium imaging of both neuronal and muscle activity, as well as systematic machine learning quantification of behaviors, makes this small cnidarian an ideal model system to understand and model the complete transformation from neural firing to body movements. To achieve this, we have built a neuromechanical model of's fluid-filled hydrostatic skeleton, showing how drive by neuronal activity activates distinct patterns of muscle activity and body column biomechanics. Our model is based on experimental measurements of neuronal and muscle activity and assumes gap junctional coupling among muscle cells and calcium-dependent force generation by muscles. With these assumptions, we can robustly reproduce a basic set of's behaviors. We can further explain puzzling experimental observations, including the dual timescale kinetics observed in muscle activation and the engagement of ectodermal and endodermal muscles in different behaviors. This work delineates the spatiotemporal control space of movement and can serve as a template for future efforts to systematically decipher the transformations in the neural basis of behavior.