Issue 3, 2015

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
07 Oct 2014
Accepted
10 Nov 2014
First published
10 Nov 2014

Lab Chip, 2015,15, 680-689

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

X. Lin, S. Wang, X. Yu, Z. Liu, F. Wang, W. T. Li, S. H. Cheng, Q. Dai and P. Shi, Lab Chip, 2015, 15, 680 DOI: 10.1039/C4LC01186D

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