Fish Fire&Wire

This project is a collaboration between researchers at Janelia Research Campus, researchers in the Molecular and Cellular Biology department at Harvard University, and a team at Google Research.

Fish Fire&Wire: A whole-brain dense connectome with function, behavior, and structure

Three institutions have worked together to generate the first vertebrate whole brain connectome and integrate it with the animal’s behavior and neural activity. Investigators at Janelia, Google, and Harvard have constructed at single synapse resolution the wiring diagram of a young behaving zebrafish. The neuronal activity of the same animal’s brain was also recorded while the animal underwent a set of behaviors. These two data sets were superimposed allowing “firing and wiring” to be directly linked. Because sensory structures and muscle outputs are included, behaviors can be tracked from sensation to action. The data is now available for analysis to all interested parties. 

Project history

This project is a collaboration between researchers at Janelia Research Campus, researchers in the Molecular and Cellular Biology department at Harvard University, and a team at Google Research. The teams performed whole-brain light-sheet imaging in a behaving zebrafish, stained, sectioned and imaged the same animal to obtain a high-throughput, high-resolution serial electron microscope volume.  Automated segmentation, synapse detection, and light-to-vEM registration pipelines were then deployed with the help of pilot manual reconstructions. The result was a reconstructed fish brain including peripheral sensory and motor structures.

Several members of this collaboration had previously participated in generating dense connectomes in multiple organisms. As a consequence, the collaboration brought together considerable experience in connectomics technology, in computational image processing for stitching, alignment and segmentation, and in human annotation to proofread and augment the automated segmentation. A group of annotators is in the process of spending ~35 proofreader years to complete the project.

The work is not yet complete but it is anticipated that a relatively complete “snapshot” of the draft connectome with associated activity data will be released by the end of July. We encourage interested researchers who seek access before publication, to do so via  the form linked below.

Key features of what will be available include:

• A whole vertebrate brain synaptic wiring diagram of a 6 day old larval zebrafish including ~140,000 neurons and their synaptic connections. In order to trace out circuits, automated access to the cohort of presynaptic and postsynaptic partners for each cell will be available.
• Neuron-level functional light-sheet imaging of the fish brain during multiple sensory, motor, cognitive, and autonomic behaviors.

• The connectivity and activity data is aligned at the individual cell level, allowing analysis of the flow of information through the brain at a cellular level of resolution.
• Beyond neurons: Because the ultrastructure includes glia, vasculature, and peripheral nervous system components, this data also provides access to the many non-neuronal components of brain tissue and peripheral sensory and motor end organs.

Key Goals:

• Mechanistic models of brain-wide dynamics (function) constrained by connectivity (structure)
• Direct tracing of information flow from sensory input to motor output
• Tests of theoretical frameworks linking structure to function
• New approaches to predicting neural activity from anatomy (and vice versa)
• Insights into neuromodulation, internal state, and brain-body interactions

Contributors

Team members (alphabetically):

• Foundational contributors: Stuart Berg, Alex Chen, Nirmala Iyer, Michal Januszewski, Christopher Knecht, Jan-Matthis Lückmann, Geoffrey Meissner, Mariela Petkova, Richard Schalek, Shinya Takemura, Juan Carlos Tapia, Yuelong Wu
• Initiating groups: Misha Ahrens (Janelia), Florian Engert (Harvard), Viren Jain (Google), Jeff Lichtman (Harvard)
• Steering committee: Misha Ahrens (Janelia), Florian Engert (Harvard), Viren Jain (Google), Wyatt Korff (Janelia), Jeff Lichtman (Harvard), Sandro Romani (Janelia)
• Early foundational biological work also by: Kristian Herrera, Liangyu Tao, Xiao Liu, Alice Wang, Gregory Davis, Krista Perks, Yasuko Isoe, Marc Duque, Vickie Wang, Nagaraju Dhanyasi, and others
• Connectomics annotation, proofreading, and project support: Brandon Canino, Michael Cook, Samantha Finley-May, Miriam Flynn, Imran Hameed, Alanna Hazlett, Gary Hopkins, Shirley Lauchies, Meghan Leonard, Charli Maldonado, Caroline Mooney, Nneoma Okeoma, Christopher Ordish, Birava Patel, Tyler Paterson, Emily Phillips, Jennifer Rivas Salinas, Ashley Scott, Louis Scuderi, Claire Smith, Satoko Takemura, Iris Talebi, Alex Thomson, JJ Walsh, Tansy Yang, and SCION undergraduate students
• Collaborating and initiating scientific groups: Larry Abbott (Columbia), Misha Ahrens (Janelia), Emre Aksay (Weill-Cornell), Martha Bagnall (Washington University), Armin Bahl (University of Konstanz), Herwig Baier (MPI), Jonathan Boulanger (Institute de la Vision), Filippo Del Bene (Institut de la Vision), Florian Engert (Harvard), Mark Fishman (Harvard University), James Fitzgerald (Northwestern University), Ann Hermundstad (Janelia), Viren Jain (Google), Vivek Jayaraman (Janelia), Jeff Lichtman (Harvard), Yu Mu (Chinese Academy of Sciences), Eva Naumann (Duke University), Michael Orger (Champalimaud), Ruben Portugues (Cornell University), Sandro Romani (Janelia), Stephan Saalfeld (Janelia), Nathaniel Sawtell (Columbia), Gregor Schuhknecht (MPI), Julie Semmelhack (Hong Kong University of Science and Technology), Srini Turaga (Janelia), Claire Wyart (INSERM), En Yang (University of North Carolina, Chapel Hill), Guoqiang Yu (Tsinghua University)

Sign up to participate, contribute, and collaborate. 

Policies

Although this work is not completed, some researchers may benefit from access to the data at this stage. We have therefore created a process for research labs to request access to the current “snapshot.” Snapshots will be periodically produced until the dataset is complete. Access is provided on the condition that papers or preprints using this data will not be submitted before December 1, 2027.

Because this access is intended for the requesting investigator and their research group, please direct other interested researchers to fill out the form rather than redistributing the data. In this way all the groups using this unpublished data are known. The aim here is to allow all groups to know what projects are taking place to encourage collaboration and openness. Because the connectome will be shared as a series of version-indexed snapshots as proofreading, synapse annotation, and cell typing improve, users should identify the snapshot version or versions used in any papers submitted.

In addition to scientific analysis the team welcomes any groups that wish to contribute more directly to the ongoing core effort, including proofreading, cell typing, debugging, annotation, or related infrastructure. Some research groups have been involved in this work from early stages, and additional groups are encouraged to contact the team to join in if interested.

As is customary, using data prior to publication comes with responsibilities related to shared authorship and, when appropriate, acknowledgment.Please discuss authorship and acknowledgment with the team before submission.