A connectomics milestone: Mapping the complete male

What happened

We partnered with HHMI Janelia and collaborators to publish a complete map of the male fruit fly’s brain and central nervous system, creating the largest brain map to date. Together with ongoing research on other species, such as fish and mice, these wiring maps begin to reveal the mechanics of how all brains work.

By 2020, our team and collaborators released a human-verified map of half a female fruit fly brain with 25,000 neurons and 21 million connections, a record at the time. Meanwhile, the team was already working on the full, verified brain map for a male fruit fly, which is now complete. These methods continue to improve.

A recent effort incorporated synthetic neurons into the training data, successfully improving the speed and accuracy of our state-of-the-art reconstruction system, PATHFINDER. We are also helping to develop new techniques for labeling and annotating specific types of neurons. Currently, mapping the fruit fly brain requires years of human effort just to verify and annotate the neural shapes.

By reducing this need for manual error correction, research groups can tackle even larger brain mapping projects within reasonable budgets and timelines. The field of connectomics is already advancing into vertebrates: organisms with a spinal cord. These are anatomically, evolutionarily and functionally more similar to humans.

In a study led by Columbia University and published this week in Nature, our team helped map a portion of the elephantnose fish’s hindbrain that is used in signal processing.

This paper, “Connectome analysis of a cerebellum-like circuit for sensory prediction”, shows for the first time how the connectome, a static resource, can be combined with other information to study neural plasticity and learning, producing the most complete mechanistic model of learning in a vertebrate brain to date.

Why it matters

The common fruit fly, Drosophila melanogaster, has been central to scientific research leading to multiple Nobel Prizes. Fruit flies have been a fundamental model organism in genetics, thanks to their stereotypical behavior and short life cycle, and promise to do the same for neuroscience. While the thoughts of this fruit-loving insect might seem far removed from human cognition, the brains of vastly different species share many similarities.

Because mapping the 86 billion neurons in a human brain is not yet possible, scientists are using AI to map the brains of smaller organisms, like fruit flies. This will help us decipher how animal nervous systems perceive the world, react to stimuli, and how damaged neural pathways might one day be repaired.

Now, in a project led by Howard Hughes Medical Institute (HHMI) Janelia Research Campus, our team and collaborators have released a complete wiring diagram of the male fruit fly’s brain and central nervous system.

Published in Cell, “Sexual dimorphism in the complete connectome of the Drosophila male central nervous system”, is the result of a decade-long partnership that advances the field of connectomics using computing and AI to build cellular-scale maps of entire brains.

With over 166,000 neurons and 125 million synaptic connections, this is the largest brain map by number of neurons to date, providing a fundamental resource for scientists to use fruit flies as a model organism for studying how the brain works.

Brain mapping, or connectomics, begins with sectioning a brain into millions of thin slices, taking an image of each section, and using computers and AI to stitch the images together. Our researchers build systems that leverage AI to turn flat electron microscope images into 3D reconstructions, using an evolving suite of techniques to generate accurate neural shapes.

Our AI connectomics tools include flood-filling networks, which use convolutional neural networks to start at a single pixel and identify all other pixels that are part of the same object. In 2019, our Connectomics team released an initial, fully-automated reconstruction of a female fruit fly brain.

What to watch

Larval zebrafish are one of the few vertebrates whose brains are small enough to be mapped from end to end using current techniques. Zebrafish also have the advantage of being transparent in their larval stage, allowing measurements of neural activity during experiments, as captured in the ZAPBench dataset.

Our upcoming paper with Harvard, “A connectomic resource for neural cataloguing and circuit dissection of the larval zebrafish brain”, is the first whole-brain dataset for a vertebrate that includes the neural structure and molecular type spanning an entire vertebrate brain. Our team also released a preliminary version of a dataset that combines neural activity and structure in the same larval zebrafish brain, as an open resource to the research community.