PreprintCited by 147Functional Brain Connectivity StudiesNeurobiology and Insect Physiology ResearchComplex Network Analysis Techniques

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Network Statistics of the Whole-Brain Connectome of Drosophila

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Abstract

Brains comprise complex networks of neurons and connections. Network analysis applied to the wiring diagrams of brains can offer insights into how brains support computations and regulate information flow. The completion of the first whole-brain connectome of an adult Drosophila , the largest connectome to date, containing 130,000 neurons and millions of connections, offers an unprecedented opportunity to analyze its network properties and topological features. To gain insights into local connectivity, we computed the prevalence of two- and three-node network motifs, examined their strengths and neurotransmitter compositions, and compared these topological metrics with wiring diagrams of other animals. We discovered that the network of the fly brain displays rich club organization, with a large population (30% percent of the connectome) of highly connected neurons. We identified subsets of rich club neurons that may serve as integrators or broadcasters of signals. Finally, we examined subnetworks based on 78 anatomically defined brain regions or neuropils. These data products are shared within the FlyWire Codex and will serve as a foundation for models and experiments exploring the relationship between neural activity and anatomical structure.

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Crossref · 10.1101/2023.07.29.551086

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  • The largest weights in the projectome tend to be internal to individual neuropils, such as within the medulla or within the fan-shaped body.

    “The largest weights in the projectome tend to be internal to individual neuropils, such as within the medulla or within the fan-shaped body49.”

    From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [49]

    The Results section, “Differences in connectivity across brain regions” (page not provided), reports high fractions of internal connection weight in the fan-shaped body and medullae, and says 52% of connection weight across the brain is internal. The Methods section defines those internal weights as entries on the projectome’s diagonal. The paper does not establish that the largest individual projectome weights tend to be internal; a high internal fraction is not the same as a ranking of the largest weights. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Most neuropils of the Drosophila brain contain one or a few large GABAergic neurons private to that neuropil, with high in degree and out degree.

    “Most neuropils of the Drosophila brain contain one or a few large GABAergic neurons private to that neuropil, with high in degree and out degree (see Lin et al.49 for further analysis on connectivity motifs); these neurons are considered to be important for local feedback gain control69.”

    From Neuronal wiring diagram of an adult brain (2024) · cites this paper as Lin et al.49

    The Results section, “Identifying neuropil-specific reciprocal neurons” (page unavailable), identifies highly connected neurons whose connections are mostly within one neuropil; 54% are GABAergic. It does not establish that most neuropils contain only one or a few such neurons: it says some contain many, and its criterion is mostly within a neuropil, not exclusively private to it. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • Lin et al. identified all GABAergic and glutamatergic neurons that are bidirectionally coupled with large numbers of cholinergic neurons.

    “Lin et al.49 identified all GABAergic and glutamatergic neurons that are bidirectionally coupled with large numbers of cholinergic neurons.”

    From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [49]

    The Results section on reciprocal connections reports that cholinergic–GABAergic pairs are the most common reciprocal pairing and cholinergic–glutamatergic pairs the second most common. The section on neuropil-specific reciprocal neurons also identifies a highly reciprocal group that includes both inhibitory types. Neither passage establishes that the authors identified all neurons of those types bidirectionally coupled with large numbers of cholinergic neurons. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • Almost every neuron in the central brain can be reached by starting from any modality.

    “We find that almost every neuron in the central brain can be reached by starting from any modality—this ‘small world’ property of the network is covered in more detail by Lin et al.49”

    From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [49]

    The Results sections on connected components and small-worldness report that 93.3% of neurons belong to one strongly connected component, with short directed paths between its neurons. This supports the cited description of broad reachability and a small-world network, but does not establish that almost every central-brain neuron is reachable when starting from each sensory modality. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • For the first time, one can now compare entire connectomes of different species, starting with D. melanogaster and C. elegans.

    “For the first time, one can now compare entire connectomes of different species, starting with D. melanogaster and C. elegans, as touched on here and explored in more depth by Lin et al.49.”

    From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [49]

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Metadata

Authors
Lin, A., Yang, R., Dorkenwald, S., Matsliah, A., Sterling, A. R., Schlegel, P., Yu, S.-C., McKellar, C. E., Costa, M., Eichler, K., Bates, A. S., Eckstein, N., Funke, J., Jefferis, G. S. X. E., & Murthy, M.
Affiliations
  • Princeton University (US)
  • MRC Laboratory of Molecular Biology (GB)
  • University of Cambridge (GB)
  • Howard Hughes Medical Institute (US)
Corresponding author
Murthy, Mala
Venue
Nature
Publisher
openRxiv
Published
2023-07-29
Volume
634
Issue
8032
Pages
153-165
ISSN
0028-0836 (ISSN-L)
OpenAlex
W4403062850
Cited by
147
References
6
Citations by year
2026: 52 · 2025: 65 · 2024: 26 · 2023: 2
FWCI
34.99
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Nature (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
Funders
  • Wellcome Trust (220343/Z/20/Z, 203261/Z/16/Z)
  • National Institute of Mental Health (RF1MH117815, RF1MH129268)
  • National Institute of Neurological Disorders and Stroke (R01NS110060, U24NS126935, R35NS111580)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
Keywords
Drosophila brain, whole-brain connectome, network motifs, rich club, recurrent connectivity, neuronal cell types, neuropil, brain network topology

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