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categories: ["minds"]categories: ["minds"]tags: ["connectome", "electron microscopy", "neuroscience", "brain mapping", "segmentation", "neural circuits"]tags: ["connectome", "electron microscopy", "neuroscience", "brain mapping", "segmentation", "neural circuits"]summary: "The mapping of complete wiring diagrams of nervous systems, from macroscale fibre tracts down to every synapse in a volume of tissue."summary: "The mapping of complete wiring diagrams of nervous systems, from macroscale fibre tracts down to every synapse in a volume of tissue."updated: "2026-07-27"updated: "2026-10-29"humanEvidence: "Synapse-resolution mapping in humans has reached one cubic millimetre of fixed cortex from a single person; complete connectomes exist only for a nematode and a fly, and no mammalian brain has been mapped in full."humanEvidence: "Synapse-resolution mapping in humans has reached one cubic millimetre of fixed cortex from a single person; complete connectomes exist only for a nematode and a fly, and no mammalian brain has been mapped in full."access: "Nothing to purchase as a service: the published datasets are freely downloadable, and the imaging and segmentation are done by a handful of consortium-scale groups."access: "Nothing to purchase as a service: the published datasets are freely downloadable, and the imaging and segmentation are done by a handful of consortium-scale groups."reversibility: "irreversible"reversibility: "irreversible"lines 21–27 → 21–276 unchanged lines not shown
"rows": [ "rows": [ { "label": "Term coined", "value": "2005" }, { "label": "Term coined", "value": "2005" }, { "label": "Primary method", "value": "Volume electron microscopy" }, { "label": "Primary method", "value": "Volume electron microscopy" }, { "label": "Resolution needed", "value": "~4–8 nm in-plane" }, { "label": "Resolution needed", "value": "~4-8 nm in-plane" }, { "label": "Complete connectomes", "value": "C. elegans, larval and adult fly" }, { "label": "Complete connectomes", "value": "C. elegans, larval and adult fly" }, { "label": "Largest mammalian volume", "value": "~1 mm³ of cortex" }, { "label": "Largest mammalian volume", "value": "~1 mm³ of cortex" }, { "label": "Data per mm³", "value": "Roughly a petabyte" } { "label": "Data per mm³", "value": "Roughly a petabyte" }lines 34–41 → 34–416 unchanged lines not shown
diffusion MRI to trace fibre bundles between brain regions in living people, and synapse-resolutiondiffusion MRI to trace fibre bundles between brain regions in living people, and synapse-resolutionconnectomics, which uses electron microscopy on fixed tissue to identify every neuron and everyconnectomics, which uses electron microscopy on fixed tissue to identify every neuron and everysynapse in a volume. The second is the one relevant to [[whole-brain-emulation]] and to circuitsynapse in a volume. The second is the one relevant to [[whole-brain-emulation]] and to circuitneuroscience, and it is destructive, slow, and — for the first time in the mid-2020s — producingneuroscience. It is destructive and slow, and since the mid-2020s it has been producing completecomplete brains.brains for the first time. The word was proposed in 2005, by analogy with the genome, for a comprehensive structuralThe word was proposed in 2005, by analogy with the genome, for a comprehensive structuraldescription of a nervous system.[^sporns2005] The practice is much older: the complete wiringdescription of a nervous system.[^sporns2005] The practice is much older: the complete wiringlines 50–58 → 50–588 unchanged lines not shown
tractography algorithms are prone to false positives at fibre crossings, and the output is atractography algorithms are prone to false positives at fibre crossings, and the output is aregion-by-region matrix rather than a circuit. The NIH Human Connectome Project, launched in 2010,region-by-region matrix rather than a circuit. The NIH Human Connectome Project, launched in 2010,produced the reference datasets for this scale and made population-level comparison of connectivityproduced the reference datasets for this scale and made population-level comparison of connectivityroutine. Macroscale maps are clinically useful — they guide electrode placement inroutine. Macroscale maps are clinically useful: they guide electrode placement in[[deep-brain-stimulation]] and inform hypotheses about psychiatric disorders as disorders of[[deep-brain-stimulation]] and inform hypotheses about psychiatric disorders as disorders ofconnectivity — but they are three orders of magnitude too coarse to identify a synapse.connectivity. They are still three orders of magnitude too coarse to identify a synapse. Synapse-resolution connectomics works from tissue that has been chemically fixed, stained withSynapse-resolution connectomics works from tissue that has been chemically fixed, stained withosmium and other heavy metals, embedded in resin, and sectioned or milled. Three imaging strategiesosmium and other heavy metals, embedded in resin, and sectioned or milled. Three imaging strategieslines 65–71 → 65–716 unchanged lines not shown
Reconstruction, not imaging, was long the bottleneck. Tracing neurites by hand through thousands ofReconstruction, not imaging, was long the bottleneck. Tracing neurites by hand through thousands ofsections is prohibitively slow; the field became tractable when convolutional segmentation models,sections is prohibitively slow; the field became tractable when convolutional segmentation models,notably the flood-filling networks developed at Google, reduced the error rate enough that humanin particular the flood-filling networks developed at Google, reduced the error rate enough that humaneffort shifted from tracing to proofreading.[^januszewski2018] Even so, the adult fly connectomeeffort shifted from tracing to proofreading.[^januszewski2018] Even so, the adult fly connectomerequired a large community of proofreaders working over years.required a large community of proofreaders working over years. lines 78–84 → 78–846 unchanged lines not shown
{ "year": "2010", "title": "Human Connectome Project", "text": "The NIH funds large-scale diffusion and functional MRI mapping in healthy adults, establishing macroscale connectomics as a standard method." }, { "year": "2010", "title": "Human Connectome Project", "text": "The NIH funds large-scale diffusion and functional MRI mapping in healthy adults, establishing macroscale connectomics as a standard method." }, { "year": "2018", "title": "Automated segmentation matures", "text": "Flood-filling networks push automated neurite tracing to error rates low enough that reconstruction of large volumes becomes practical." }, { "year": "2018", "title": "Automated segmentation matures", "text": "Flood-filling networks push automated neurite tracing to error rates low enough that reconstruction of large volumes becomes practical." }, { "year": "2020", "title": "Fly hemibrain", "text": "A Janelia Research Campus team releases a dense reconstruction of about 25,000 neurons in the central brain of Drosophila, with synaptic connectivity." }, { "year": "2020", "title": "Fly hemibrain", "text": "A Janelia Research Campus team releases a dense reconstruction of about 25,000 neurons in the central brain of Drosophila, with synaptic connectivity." }, { "year": "2023", "title": "Larval fly brain", "text": "Winding and colleagues publish the complete synaptic connectome of a Drosophila larva, roughly 3,000 neurons — the first whole brain of an insect." }, { "year": "2023", "title": "Larval fly brain", "text": "Winding and colleagues publish the complete synaptic connectome of a Drosophila larva, roughly 3,000 neurons: the first whole brain of an insect." }, { "year": "2024", "title": "Human cortical millimetre", "text": "Shapson-Coe, Lichtman, Jain and colleagues release H01, a cubic millimetre of human temporal cortex containing tens of thousands of cells and around 150 million synapses in about 1.4 petabytes of imagery." }, { "year": "2024", "title": "Human cortical millimetre", "text": "Shapson-Coe, Lichtman, Jain and colleagues release H01, a cubic millimetre of human temporal cortex containing tens of thousands of cells and around 150 million synapses in about 1.4 petabytes of imagery." }, { "year": "2024", "title": "Adult fly connectome", "text": "The FlyWire consortium publishes the wiring diagram of an entire adult fruit fly brain, roughly 140,000 neurons, together with cell-type annotation." }, { "year": "2024", "title": "Adult fly connectome", "text": "The FlyWire consortium publishes the wiring diagram of an entire adult fruit fly brain, roughly 140,000 neurons, together with cell-type annotation." }, { "year": "2025", "title": "MICrONS mouse cortex", "text": "A cubic millimetre of mouse visual cortex is published with structural reconstruction co-registered to prior functional imaging of the same neurons." } { "year": "2025", "title": "MICrONS mouse cortex", "text": "A cubic millimetre of mouse visual cortex is published with structural reconstruction co-registered to prior functional imaging of the same neurons." }lines 87–94 → 87–942 unchanged lines not shown
## What has been mapped## What has been mapped Complete connectomes exist for *C. elegans* — including both sexes and several developmentalComplete connectomes exist for *C. elegans* (including both sexes and several developmentalstages — for the *Drosophila* larva, whose roughly 3,000 neurons were mapped in 2023,[^winding2023]stages), for the *Drosophila* larva, whose roughly 3,000 neurons were mapped in 2023,[^winding2023]and for the adult fruit fly. The fly is the important milestone: an animal with courtship, learning,and for the adult fruit fly. The fly is the important milestone: an animal with courtship, learning,navigation, and flight, whose full synaptic wiring is now a downloadablenavigation, and flight, whose full synaptic wiring is now a downloadabledataset.[^dorkenwald2024] Partial but dense reconstructions exist for larval zebrafish and for thedataset.[^dorkenwald2024] Partial but dense reconstructions exist for larval zebrafish and for thelines 103–109 → 103–1098 unchanged lines not shown
```keyfacts```keyfacts[[ { "value": "~140,000", "label": "Neurons in the adult fly connectome", "note": "FlyWire, 2024 — the first whole brain of a behaviourally complex animal" }, { "value": "~140,000", "label": "Neurons in the adult fly connectome", "note": "FlyWire, 2024; the first whole brain of a behaviourally complex animal" }, { "value": "~1.4 PB", "label": "Data for 1 mm³ of human cortex", "note": "H01 dataset, 2024" }, { "value": "~1.4 PB", "label": "Data for 1 mm³ of human cortex", "note": "H01 dataset, 2024" }, { "value": "~10⁶", "label": "Cubic millimetres in a human brain", "note": "Linear extrapolation puts a whole-brain dataset near a zettabyte" } { "value": "~10⁶", "label": "Cubic millimetres in a human brain", "note": "Linear extrapolation puts a whole-brain dataset near a zettabyte" }]]lines 114–131 → 114–1314 unchanged lines not shown
The human-brain arithmetic is unforgiving. A cubic millimetre at electron-microscope resolutionThe human-brain arithmetic is unforgiving. A cubic millimetre at electron-microscope resolutiongenerates on the order of a petabyte; a human brain is roughly a million cubic millimetres. Lineargenerates on the order of a petabyte; a human brain is roughly a million cubic millimetres. Linearextrapolation gives a dataset near a zettabyte, comparable to a substantial fraction of global dataextrapolation gives a dataset near a zettabyte, comparable to a substantial fraction of global datastorage, before any of it is segmented. Imaging time scales similarly. Progress on this is real —storage, before any of it is segmented. Imaging time scales similarly. Progress on this is real:multi-beam electron microscopes, faster milling, better compression, and cheaper segmentation havemulti-beam electron microscopes, faster milling, better compression, and cheaper segmentation haveeach moved throughput by large factors — but the gap is six orders of magnitude, and no announcedeach moved throughput by large factors. But the gap is six orders of magnitude, and no announcedinstrument closes it.instrument closes it. Alternative strategies aim to sidestep the imaging cost entirely. Sequencing-based approachesAlternative strategies aim to sidestep the imaging cost entirely. Sequencing-based approachesdeveloped in Anthony Zador's group tag individual neurons with random RNA barcodes and read outdeveloped in Anthony Zador's group tag individual neurons with random RNA barcodes and read outprojections by sequencing rather than imaging, trading synapse-level detail for throughput.projections by sequencing rather than imaging, trading synapse-level detail for throughput.[[george-church]] and collaborators have proposed related molecularly annotated schemes. Synchrotron X-ray[[george-church]] and collaborators have proposed related molecularly annotated schemes. Synchrotrontomography can survey large volumes of stained tissue at coarser resolution without sectioningX-ray tomography can survey large volumes of stained tissue at coarser resolution without sectioningthem, which is useful for targeting where to slice. None of these yields a synapse-level map of a mammalianthem, which is useful for targeting where to slice. None of these yields a synapse-level map of abrain.mammalian brain. ## Why a wiring diagram is not a mind## Why a wiring diagram is not a mind lines 140–168 → 140–1688 unchanged lines not shown
The nematode is the standing test of what a wiring diagram is worth, and the test has not beenThe nematode is the standing test of what a wiring diagram is worth, and the test has not beenpassed. Its 302 neurons have been mapped since 1986, and four decades of effort have not produced apassed. Its 302 neurons have been mapped since 1986, and four decades of effort have not produced asimulation that reproduces the animal's behavioural repertoire — the missing quantities beingsimulation that reproduces the animal's behavioural repertoire. The missing quantities areexactly synaptic sign and strength and the extrasynaptic neuropeptide signalling that reconfiguresexactly synaptic sign and strength and the extrasynaptic neuropeptide signalling that reconfiguresthe circuit. No connectome of any animal has yet been used to reproduce that animal's behaviour.the circuit. No connectome of any animal has yet been used to reproduce that animal's behaviour. A widely cited demonstration of the limit comes from outside biology. Eric Jonas and Konrad KordingA widely cited demonstration of the limit comes from outside biology. Eric Jonas and Konrad Kordingapplied standard neuroscience analyses, including a complete connectome, to a 6502 microprocessorapplied standard neuroscience analyses, including a complete connectome, to a 6502 microprocessorrunning video games and found that the methods failed to recover how the chip works.[^jonas2017]running video games and found that the methods failed to recover how the chip works.[^jonas2017]The point is not that connectomes are useless — they are the substrate on which every circuitThis does not make connectomes useless, since they are the substrate on which every circuithypothesis is built — but that structure underdetermines function.hypothesis is built; it shows that structure underdetermines function. > [!caution] One brain, one time point> [!caution] One brain, one time point> Every published whole-animal connectome is a snapshot. The fly datasets each come from a single> Every published whole-animal connectome is a snapshot. The fly datasets each come from a single> individual fixed at a single moment; the nematode reconstruction was assembled from sections of> individual fixed at a single moment; the nematode reconstruction was assembled from sections of> more than one animal, so it is a composite rather than any one worm's wiring. Variation between> more than one animal, so it is a composite rather than any one worm's wiring. Variation between> individuals of the same species is substantial in mammals and non-trivial even in flies, and> individuals of the same species is substantial in mammals and non-trivial even in flies, and> synapses turn over on timescales of days. A connectome is a snapshot, not a constant.> synapses turn over on timescales of days. ## Applications## Applications Circuit neuroscience is the immediate beneficiary. Fly connectome data has already been used toCircuit neuroscience is the immediate beneficiary. Fly connectome data has already been used topredict responses of unrecorded neurons and to identify circuits for specific behaviours, withpredict responses of unrecorded neurons and to identify circuits for specific behaviours, withpredictions tested by [[optogenetics]] and electrophysiology. In mammals, dense reconstruction haspredictions tested by [[optogenetics]] and electrophysiology. In mammals, dense reconstruction hasrevealed connectivity rules — which cell types contact which, and how selectively — that sparserevealed connectivity rules (which cell types contact which, and how selectively) that sparserecording could not establish. Structural priors of this kind feed back into applied work:recording could not establish. Structural priors of this kind feed back into applied work:population models used in [[neural-decoding]] and in [[brain-computer-interface]] research, andpopulation models used in [[neural-decoding]] and in [[brain-computer-interface]] research, andcircuit models of the hippocampus underlying attempts at a [[memory-prosthesis]], all depend oncircuit models of the hippocampus underlying attempts at a [[memory-prosthesis]], all depend onlines 173–191 → 173–1914 unchanged lines not shown
Connectomics also underwrites the argument for [[brain-preservation]]: if the connectome plusConnectomics also underwrites the argument for [[brain-preservation]]: if the connectome plusmolecular annotation is the information that matters, then a preservation method that demonstrablymolecular annotation is the information that matters, then a preservation method that demonstrablyretains it converts death into a storage problem. Whether that "if" is true is exactly what theretains it converts death into a storage problem. Whether that "if" is true is exactly what theBargmann–Marder objection challenges, and it bears directly on [[cryonics]], onBargmann-Marder objection challenges, and it bears directly on [[cryonics]], on[[mind-uploading]], and on what would have to survive for the preserved person to survive with it,[[mind-uploading]], and on what would have to survive for the preserved person to survive with it,a question treated under [[personal-identity-and-continuity]]. Nothing in current connectomicsa question treated under [[personal-identity-and-continuity]]. Nothing in current connectomicssettles which level of detail an emulation would need.settles which level of detail an emulation would need. ## Outlook## Outlook The stated near-term targets are a whole mouse brain at synapse resolution — an effort severalThe stated near-term targets are a whole mouse brain at synapse resolution and larger human corticalgroups and funders, including the US BRAIN Initiative, have framed as the next milestone — andvolumes with molecular labelling. Several groups and funders, including the US BRAIN Initiative,larger human cortical volumes with molecular labelling. A mouse brain is roughly a thousand timeshave framed the mouse brain as the next milestone. A mouse brain is roughly a thousand times thethe volume already reconstructed and would be the first mammalian connectome in full. Whether itvolume already reconstructed and would be the first mammalian connectome in full. Whether it arrivesarrives in the 2030s depends less on microscopes than on segmentation cost and on whether fundersin the 2030s depends less on microscopes than on segmentation cost and on whether funders sustain asustain a project whose output is a dataset rather than a discovery.project whose output is a dataset rather than a discovery. ## See also## See also removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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