@article {70084,
	title = {Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits},
	journal = {bioRxiv},
	year = {2025},
	month = {2025 August 22},
	abstract = {<p>All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors1,2. Physiology seeks to elucidate the intricate network of interactions that sustain life, which often span multiple organs, cell types, and timescales, but a major challenge lies in the inability to simultaneously record time-varying cellular activity throughout the entire body.We developed WHOLISTIC, a method to image second-timescale, time-varying intracellular dynamics across cell-types of the vertebrate body. By advancing and integrating volumetric fluorescence microscopy, machine learning, and pancellular transgenic expression of calcium sensors in transparent young Danio rerio (zebrafish) and adult Danionella, the method enables real-time recording of cellular dynamics across the organism. Calcium is a universal intracellular messenger, with a large array of cellular processes depending on changes in calcium concentration across varying time-scales, making it an ideal proxy of cellular activity3.Using this platform to screen the dynamics of all cells in the body, we discovered unexpected responses of specific cell types to stimuli, such as chondrocyte reactions to cold, meningeal responses to ketamine, and state-dependent activity, such as oscillatory ependymal-cell activity during periods of extended motor quiescence. At the organ scale, the method uncovered pulsating traveling waves along the kidney nephron. At the multi-organ scale, we uncovered muscle synergies and independencies, as well as muscle-organ interactions. Integration with optogenetics allowed us to all-optically determine the causal direction of brain-body interactions. At the whole-organism scale, the method captured the rapid brainstem-controlled redistribution of blood flow across the body.Finally, we advanced Whole-Body Expansion Microscopy4 to provide ground-truth molecular and ultrastructural anatomical context, explaining the spatiotemporal structure of activity captured by WHOLISTIC. Together, these innovations establish a new paradigm for systems biology, bridging cellular and organismal physiology, with broad implications for both fundamental research and drug discovery.</p>
},
	doi = {10.1101/2025.08.20.670374},
	url = {https://www.biorxiv.org/content/early/2025/08/22/2025.08.20.670374.1},
	author = {Ruetten, Virginia M. S. and Zheng, Wei and Siwanowicz, Igor and Mensh, Brett D. and Eddison, Mark and Hu, Amy and Chi, Yunfeng and Lemire, Andrew L. and Guo, Caiying and Kadobianskyi, Mykola and Renz, Marc and Lelek-Greskovic, Sara and He, Yisheng and Close, Kari and Ihrke, Gudrun and Dev, Aparna and Petruncio, Alyson and Wan, Yinan and Engert, Florian and Fishman, Mark C. and Judkewitz, Benjamin and Rubinov, Mikail and Keller, Philipp J. and Satou, Chie and Yu, Guoqiang and Tillberg, Paul W. and Sahani, Maneesh and Ahrens, Misha B.}
}
@article {49545,
	title = {Imaging cortical dynamics in GCaMP transgenic rats with a head-mounted widefield macroscope.},
	journal = {Neuron},
	year = {2018},
	month = {2018 Oct 22},
	abstract = {<p>Widefield imaging of calcium dynamics is an emerging method for mapping regional neural activity but is currently limited to restrained animals. Here we describe cScope, a head-mounted widefield macroscope\&nbsp;developed to image large-scale cortical dynamics in rats during natural behavior. cScope provides a 7.8\&nbsp;{\texttimes} 4\&nbsp;mm field of view and dual illumination paths for both fluorescence and hemodynamic correction and can be fabricated at low cost using readily attainable components. We also report the development of Thy-1 transgenic rat strains with widespread neuronal expression of the calcium indicator GCaMP6f. We combined these two technologies to image large-scale calcium dynamics in the dorsal neocortex during a visual evidence accumulation\&nbsp;task. Quantitative analysis of task-related dynamics revealed multiple regions having neural signals that encode behavioral choice and sensory evidence. Our results provide a new transgenic resource for calcium imaging in rats and extend the domain of head-mounted microscopes to larger-scale cortical dynamics.</p>
},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2018.09.050},
	author = {Scott, Benjamin B and Thiberge, Stephan Y and Guo, Caiying and Tervo, D Gowanlock R and Brody, Carlos D and Karpova, Alla Y and Tank, David W}
}
