High-throughput mapping of brain-wide activity in awake and drug-responsive vertebrates

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 be...

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Bibliographic Details
Published in:Lab on a chip 2015-02, Vol.15 (3), p.680-689
Main Authors: Lin, Xudong, Wang, Shiqi, Yu, Xudong, Liu, Zhuguo, Wang, Fei, Li, Wai Tsun, Cheng, Shuk Han, Dai, Qiuyun, Shi, Peng
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - drug effects
Behavior, Animal - physiology
Brain
Brain - drug effects
Brain - physiology
Brain Mapping
Circuits
High-Throughput Screening Assays
Larva
Mapping
Microfluidic Analytical Techniques
Microfluidics
Neurotoxins - pharmacology
Peptides - pharmacology
Toxins
Vertebrates
Wakefulness - physiology
Zebrafish
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Summary: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.
ISSN:1473-0197
1473-0189
DOI:10.1039/c4lc01186d