Selected Grantee Publications
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- 9 results found
- Aquatic Vertebrate Models
- R43/R44 [SBIR]
Gigapixel Imaging With a Novel Multi-Camera Array Microscope
Thomson et al., eLife. 2022.
https://www.doi.org/10.7554/eLife.74988
The dynamics of living organisms are organized across many spatial scales. The investigators created assembled a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution, large field-of-view recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, they computationally generated gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This system allows the team to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales (e.g., larval zebrafish, fruit flies, slime mold). Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms. Supported by ORIP (R44OD024879), NIEHS, NCI, and NIBIB.
A Novel Wireless ECG System for Prolonged Monitoring of Multiple Zebrafish for Heart Disease and Drug Screening Studies
Le et al., Biosensors and Bioelectronics. 2022.
https://pubmed.ncbi.nlm.nih.gov/34801796/
Zebrafish and their mutant lines have been extensively used in cardiovascular studies. In the current study, the novel system Zebra II is presented for prolonged electrocardiogram (ECG) acquisition and analysis for multiple zebrafish within controllable working environments. The Zebra II is composed of a perfusion system, apparatuses, sensors, and an in-house electronic system. First, the Zebra II is validated in comparison with a benchmark system, namely iWORX, through various experiments. The validation displayed comparable results in terms of data quality and ECG changes in response to drug treatment. The effects of anesthetic drugs and temperature variation on zebrafish ECG were subsequently investigated in experiments that need real-time data assessment. The Zebra II's capability of continuous anesthetic administration enabled prolonged ECG acquisition up to 1 h compared to that of 5 min in existing systems. The novel cloud-based automated analysis with data obtained from four fish further provided a useful solution for combinatorial experiments and helped save significant time and effort. The system showed robust ECG acquisition and analytics for various applications, including arrhythmia in sodium-induced sinus arrest, temperature-induced heart rate variation, and drug-induced arrhythmia in Tg(SCN5A-D1275N) mutant and wildtype fish. The multiple channel acquisition also enabled the implementation of randomized controlled trials on zebrafish models. The developed ECG system holds promise and solves current drawbacks in order to greatly accelerate drug screening applications and other cardiovascular studies using zebrafish. Supported by ORIP (R44OD024874) and NHLBI.
Functional and Ultrastructural Analysis of Reafferent Mechanosensation in Larval Zebrafish
Odstrcil et al., Current Biology. 2022.
https://www.sciencedirect.com/science/article/pii/S096098222101530X
All animals need to differentiate between exafferent stimuli (caused by the environment) and reafferent stimuli (caused by their own movement). Researchers characterized how hair cells in zebrafish larvae discriminate between reafferent and exafferent signals. Dye labeling of the lateral line nerve and functional imaging was combined with ultra-structural electron microscopy circuit reconstruction to show that cholinergic signals originating from the hindbrain transmit efference copies, and dopaminergic signals from the hypothalamus may affect threshold modulation. Findings suggest that this circuit is the core implementation of mechanosensory reafferent suppression in these young animals. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Precise Visuomotor Transformations Underlying Collective Behavior in Larval Zebrafish
Harpaz et al., Nature Communications. 2021.
https://www.nature.com/articles/s41467-021-26748-0
Sensory signals from neighbors, analyzed in the visuomotor stream of animals, is poorly understood. The authors studied aggregation behavior in larval zebrafish and found that over development larvae transition from over dispersed groups to tight shoals. Young larvae turn away from virtual neighbors by integrating and averaging retina-wide visual occupancy within each eye, and by using a winner-take-all strategy for binocular integration. Observed algorithms accurately predict group structure over development. These findings allow testable predictions regarding the neuronal circuits underlying collective behavior in zebrafish. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Collective Behavior Emerges from Genetically Controlled Simple Behavioral Motifs in Zebrafish
Harpaz et al., Science Advances. 2021.
https://www.science.org/doi/10.1126/sciadv.abi7460
Harpaz et al. report that zebrafish regulate their proximity and alignment with each other at early larval stages. Two visual responses (one measuring relative visual field occupancy and one accounting for global visual motion), account for emerging group behavior. Mutations in genes known to affect social behavior in humans perturb these reflexes in individual larval zebrafish and change their emergent collective behaviors. Model simulations show that changes in these two responses in individual mutant animals predict well the distinctive collective patterns that emerge in a group. Hence, group behaviors reflect in part genetically defined primitive sensorimotor “motifs” evident in young larvae. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Deep Learning-Based Framework for Cardiac Function Assessment in Embryonic Zebrafish from Heart Beating Videos
Naderi et al., Computers in Biology and Medicine. 2021.
https://www.sciencedirect.com/science/article/pii/S0010482521003590
Zebrafish is a powerful model system for a host of biological investigations, cardiovascular studies, and genetic screening. However, the current methods for quantifying and monitoring zebrafish cardiac functions involve tedious manual work and inconsistent estimations. Naderi et al. developed a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) based on a U-net deep learning model for automated assessment of cardiovascular indices, such as ejection fraction (EF) and fractional shortening (FS) from microscopic videos of wildtype and cardiomyopathy mutant zebrafish embryos. The framework could be widely applicable with any laboratory resources, and the automatic feature holds promise to enable efficient, consistent, and reliable processing and analysis capacity. Supported by ORIP (R44OD024874)
Algorithms Underlying Flexible Phototaxis in Larval Zebrafish
Chen et al., Journal of Experimental Biology. 2021.
https://pubmed.ncbi.nlm.nih.gov/34027982/
Given that physiological and environmental variables undergo constant fluctuations over time, how do biological control systems maintain control over these values? The authors demonstrate that larval zebrafish use phototaxis to maintain environmental luminance at a set point, that the value of this set point fluctuates on a time scale of seconds when environmental luminance changes, and it is determined by calculating the mean input across both sides of the visual field. Feedback from the surroundings drives allostatic changes to the luminance set point. The authors describe a novel behavioral algorithm with which larval zebrafish exert control over a sensory variable. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Larval Zebrafish Use Olfactory Detection of Sodium and Chloride to Avoid Salt Water
Herrera et al., Current Biology. 2021.
https://pubmed.ncbi.nlm.nih.gov/33338431/
Zebrafish are freshwater fish unable to tolerate high-salt environments and would benefit from neural mechanisms that enable the navigation of salt gradients to avoid high salinity. Yet zebrafish lack epithelial sodium channels, the primary conduit land animals use to taste sodium. This suggests fish may possess novel, undescribed mechanisms for salt detection. In the present study, the authors show that zebrafish indeed respond to small temporal increases in salt by reorienting more frequently. In summary, this study establishes that zebrafish larvae can navigate and thus detect salinity gradients and that this is achieved through previously undescribed sensory mechanisms for salt detection. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Acoustofluidic Rotational Tweezing Enables High-Speed Contactless Morphological Phenotyping of Zebrafish Larvae
Chen et al., Nature Communications. 2021.
https://pubmed.ncbi.nlm.nih.gov/33602914/
These authors demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae enabling multispectral imaging of the zebrafish body and internal organs. They developed a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation. With its contactless nature and advantages in speed and automation, the acoustofluidic rotational tweezing system has the potential to be a valuable asset for developmental biology and pre-clinical drug development in pharmacology. Supported by ORIP (R43OD024963), NCI, and NIGMS.