title: High-throughput mapping of brain-wide activity in awake and drug-responsive vertebrates.
abstract: 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.
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Ave, Kowloon, Hong Kong SAR, China 999077. pengshi@cityu.edu.hk.
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.forename: Shiqi
authors.initials: S
authors.lastname: Wang
authors.forename: Xudong
authors.initials: X
authors.lastname: Yu
authors.forename: Zhuguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Wai Tsun
authors.initials: WT
authors.lastname: Li
authors.forename: Shuk Han
authors.initials: SH
authors.lastname: Cheng
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Dai
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D057166:High-Throughput Screening Assays; D007814:Larva; D046210:Microfluidic Analytical Techniques; D009498:Neurotoxins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology*; D015027:Zebrafish
chemical_list: D009498:Neurotoxins; D010455:Peptides