期刊
LAB ON A CHIP
卷 15, 期 3, 页码 680-689出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4lc01186d
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资金
- National Science Foundation of China [81201164]
- University Grants Council of Hong Kong [ECS125012, GRF11211314]
- Innovation and Technology Commission of Hong Kong [ITF3 ITS/376/13]
- City University of Hong Kong [7200269, 9610215, 9667077, 7003022]
The reconstruction of neural activity across complete neural circuits, or brain activity mapping, has great potential in both fundamental and translational neuroscience research. Larval zebrafish, a vertebrate model, has recently been demonstrated to be amenable to whole brain activity mapping in behaving animals. Here we demonstrate a microfluidic array system (Fish-Trap) that enables high-throughput mapping of brain-wide activity in awake larval zebrafish. Unlike the commonly practiced larva-processing methods using a rigid gel or a capillary tube, which are laborious and time-consuming, the hydrodynamic design of our microfluidic chip allows automatic, gel-free, and anesthetic-free processing of tens of larvae for microscopic imaging with single-cell resolution. Notably, this system provides the capability to directly couple pharmaceutical stimuli with real-time recording of neural activity in a large number of animals, and the local and global effects of pharmacoactive drugs on the nervous system can be directly visualized and evaluated by analyzing drug-induced functional perturbation within or across different brain regions. Using this technology, we tested a set of neurotoxin peptides and obtained new insights into how to exploit neurotoxin derivatives as therapeutic agents. The novel and versatile Fish-Trap technology can be readily unitized to study other stimulus (optical, acoustic, or physical) associated functional brain circuits using similar experimental strategies.
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