RoLi Lab article published in Nature Methods online publication

September 11, 2017
RoLi Lab article published in Nature Methods online publication

The RoLi Lab has developed a microscope that allows neuroscientists to record the activity of every neuron in a fish brain while the animal is freely swimming and interacting with the world. This work expands the repertoire of natural behaviors that can be studied with cellular resolution calcium imaging, including spatial navigation, social behavior, feeding and reward.

Kim DH, Kim J, Marques JC, Grama A, Hildebrand DGC, Gu W, Li JM, Robson DN. Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish. Nature Methods Advance Online Publication (doi:10.1038/nmeth.4429)

Summary

Scientists have made tremendous progress in recent years to produce bigger and better datasets of brain activity and structure. However, the “purpose” of all that complexity in the brain can only be understood in the context of animal behavior. Exactly when and how neurons fire can depend on the animal’s interactions with the world, both past and present. Out of necessity, however, scientists have often had to restrict the animal’s behavior to obtain high quality recordings of brain activity: most microscopes can’t move, so the animal must sit still. For scientists working with larval zebrafish, this generally means either plunking the animal into a blob of agarose, essentially embedding it in Jell-O, or paralyzing the animal altogether. The animal can’t fully swim, eat, hide, or socialize. Neuroscientists are thus blind to much of the neural activity that drives these essential behaviors. The RoLi Lab sought to remedy this by developing a tracking microscope that frees the larval zebrafish to do many of these behaviors.

Tracking microscopes are a broad class of microscopes that can follow an animal in motion. The first was invented in 1971 by Howard Berg to study the movements of bacteria, and led him to describe the biased random walk, one of the most fundamental insights into bacterial motion. Since then, tracking microscopes have been developed for C. elegans and Drosophila larvae, and have helped to elucidate the neural basis of navigational behavior. However, larval zebrafish were particularly challenging due to their impressive speed. A larval zebrafish has a peak velocity of 200 mm/s, and a peak acceleration of 20,000 mm/s^2, similar to the acceleration of a Formula One race car.

To overcome these challenges, the RoLi lab has developed for the first time a tracking microscope that uses optimal control theory to keep pace with larval zebrafish. Using this microscope, the RoLi lab has demonstrated that neural activity throughout the larval zebrafish brain can be recorded at single cell resolution while the animal is freely engaged in navigation, hunting, and feeding.

Finally, by allowing animals to freely engage with their environment during imaging, the tracking microscope opens up the possibility of continuous observation of neural activity on the longer timescales in which animals grow and learn.

 

 

Article citation:

Kim DH, Kim J, Marques JC, Grama A, Hildebrand DGC, Gu W, Li JM, Robson DN. Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish. Nature Methods Advance Online Publication (doi:10.1038/nmeth.4429)

 

Article link:

http://rdcu.be/vKdi