What is a connectome? The wiring map of a brain

Short answer: A connectome, or wiring map, is the complete list of neurons in a nervous system and the synaptic connections between them: which neuron connects to which, and through how many synapses. The brain is imaged with an electron microscope in thousands of thin layers, AI traces the neurons, and researchers fix the mistakes by hand. The largest complete maps so far belong to the fruit fly.

How is it made?

  1. The brain is imaged with an electron microscope in layers a few nanometres thick.
  2. The images are aligned into a three-dimensional volume.
  3. Machine learning marks the boundaries of every neuron and the synapses.
  4. People correct the errors (FlyWire also drew in volunteers from around the world).
  5. Neurons are sorted into cell types by their shape and connections.

The effort is enormous: the 2020 map of half a fly brain (the hemibrain) took more than 50 person-years of proofreading, turning over 20 terabytes of images into a connection table of a few tens of megabytes.

Milestones

What a map tells you, and what it doesn't

A wiring map shows which neuron connects to which and through how many synapses. Researchers use it to form ideas about how a circuit might work and to aim their experiments.

There is also much it does not show on its own. The number of synapses is only a rough measure of a connection's strength. Whether a connection excites or inhibits is inferred from the chemical the neuron releases. The effects of neuromodulators such as dopamine and serotonin, weights that change with learning, and differences between individuals are invisible in the map, and electrical synapses are hard to detect in electron microscope images. Knowing a city's road map is not the same as knowing its traffic: you see the roads, not the cars.

Why the fruit fly?

The fruit fly has been one of biology's most studied animals for over a century. Genetic tools that switch specific neurons on and off, rich behaviour such as learning, navigation and courtship, and a brain small enough to map make it possible to study behaviour and circuits in the same animal.

Sources

  1. White JG, Southgate E, Thomson JN, Brenner S (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. B 314: 1–340. https://openworm.org/ConnectomeToolbox/White_1986/
  2. Scheffer LK et al. (2020). A connectome and analysis of the adult Drosophila central brain. eLife 9: e57443. https://elifesciences.org/articles/57443
  3. Winding M. et al. (2023). The connectome of an insect brain. Science 379.
  4. Dorkenwald S. et al. (2024). Neuronal wiring diagram of an adult brain. Nature. https://pmc.ncbi.nlm.nih.gov/articles/PMC11446842
  5. Janelia FlyEM and partners: Male CNS connectome (MaleCNS), CC BY 4.0. https://male-cns.janelia.org/

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