By Ashwin Bhandiwad, PhD
The NICHD, in collaboration with the International Zebrafish Society, hosted the International Workshop on Zebrafish Neural Circuits and Behavior, a three-day meeting that took place November 15-17, 2017, at the Neuroscience Center Building in Rockville, Maryland. The event followed the annual Society for Neuroscience meeting in Washington, D.C., and was attended by around 170 principal investigators, postdoctoral researchers, and graduate students from 19 countries.
The meeting was designed to highlight novel and unpublished research in zebrafish behavior, physiology, and neuroanatomy, with a special focus on methods and tool development. This refined focus made it possible to explore the primary questions in the field with greater depth.
The emphasis on unpublished data not only facilitated discussions about novel methods, but also led to collaborative discussions between labs to implement these new techniques. Due to space constraints, the meeting had a strict attendance limit. However, postdocs at the NICHD volunteered at the meeting and had the unique opportunity to attend the workshops and build professional ties with investigators who presented their newest data.
Following opening comments from NICHD’s Dr. Harold Burgess, one of the hosts of the workshop, speakers presented new genetic tools to label, visualize, and manipulate distinct neuronal populations. These tools expand the types of experiments that can be conducted using zebrafish. For example, newly developed fluorescent indicators have a high spatial and temporal resolution, facilitating precise, noninvasive monitoring of neural activity during early functional development.
Topics covered over the next few days included:
- How circuits drive motivated and social behaviors
- Learning and memory
- Sensory systems and their functional development
A major focus of the conference was the grand challenge of mapping the entire brain of a five-day-old zebrafish at the single cell level. By this stage of development, zebrafish have a fully functioning central nervous system with a relatively small number of neurons (approximately a million times fewer than in humans), which makes whole-brain connectivity mapping possible with current technologies. Solving challenges in whole brain mapping on this small scale will provide a roadmap for solving this problem in larger vertebrates with more complex brains, including humans.
The meeting also hosted a workshop to combine and standardize newly developed tools in brain imaging and registration for general use in the zebrafish community. Brain registration is a technique by which an imaged brain is algorithmically mapped onto a model of a brain, creating a standardized reference that can be compared across multiple individuals. Research groups discussed how to share data and build a working system to incorporate imaging data from multiple labs into a centralized database of registered brains. These databases would contain whole brain images from transgenic animals as well as individual neuron tracings all mapped onto a model. This would aid in a direct comparison between brain regions and improve experimental design for experimental manipulations in the future. The workshop was the first step toward establishing this kind of database.
What types of new experiments could brain registration facilitate? One goal is to map the neurons driving specific behaviors, such as tracking prey. On the final day of the meeting, multiple groups presented new microscopy techniques using a conventional camera with a volumetric fluorescent microscope and automatic tracking. This set up, combined with larval fish that are genetically modified to show increased fluorescence upon neural activation, allowed groups to measure neural activity across the entire brain of a fish during a target behavior. The brain registration database would allow for brain mapping comparison between groups.
Many attendees remarked on the rapid progress that has been made in developing sophisticated methods for probing brain structure and function. New results are finally answering questions posed over a century ago. Volunteering at this particular meeting was a great opportunity for NICHD fellows, as the meeting offered a peek at the future of zebrafish neural research—even before many of the discussed techniques reach publication. Although some of these techniques are already in use within NICHD labs, this meeting gave NICHD fellows in attendance a new perspective about how labs are approaching similar questions, which provides critical insight going forward.
A common comment heard throughout the meeting was that some of these experiments would have been impossible to do five years ago. The stage seems set for even greater advances in the next five.