Journal Article

Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (Danio rerio)

Wang, Zeguan, Wen, Quan, Chai, Yuming, Hang, Wei, Yang, Wenbin, Du, Jiulin, Bai, Lu, Shang, Chunfeng, Wang, Kai, Cong, Lin

2017

Overview

The internal brain dynamics that link sensation and action are arguably better studied during natural animal behaviors. Here, we report on a novel volume imaging and 3D tracking technique that monitors whole brain neural activity in freely swimming larval zebrafish (Danio rerio). We demonstrated the capability of our system through functional imaging of neural activity during visually evoked and prey capture behaviors in larval zebrafish. How do neurons in the brain process information from the senses and drive complex behaviors? This question has fascinated neuroscientists for many years. It is currently not possible to record the electrical activities of all of the 100 billion neurons in a human brain. Yet, in the last decade, it has become possible to genetically engineer some neurons in animals to produce fluorescence reporters that change their brightness in response to brain activity and then monitor them under a microscope. In small animals such as zebrafish larvae, this method makes it possible to monitor the activities of all the neurons in the brain if the animal’s head is held still. However, many behaviors – for example, catching prey – require movement, and no existing technique could image brain activity in enough detail if the animal’s head was moving. Cong, Wang, Chai, Hang et al. have now made progress towards this goal by developing a new technique to image neural activity across the whole brain of a zebrafish larva as it swims freely in a small water-filled chamber. The technique uses high-speed cameras and computer software to track the movements of the fish in three dimensions, and then automatically moves the chamber under the microscope such that the animal’s brain is constantly kept in focus. The newly developed microscope can capture changes in neural activity across a large volume all at the same time. It is then further adapted to overcome problems caused by sudden or swift movements, which would normally result in motion blur. With this microscope set up, Cong et al. were able to capture, for the first time, activity from all the neurons in a zebrafish larva’s brain as it pursued and caught its prey. This technique provides a new window into how brain activity changes when animals are behaving naturally. In the future, this technique could help link the activities of neurons to different behaviors in several popular model organisms including fish, worms and fruit flies.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: 3D tracking system / Animals / Behavior / Behavior, Animal / Brain - physiology / Danio rerio / Experiments / freely behaving larval zebrafish / Imaging, Three-Dimensional - methods / Laboratories / Larva - physiology / Light / light field microscope / Medical imaging / Microscopy / Neuroimaging / Neuroimaging - methods / Neurons / Neuroscience / Neurosciences / Prey / prey capture behavior / Science / Swimming / Tools and Resources / Virtual reality / whole brain Imaging / Zebrafish / Zebrafish - physiology