The fly connectome reveals a path to the effectome
Open accessAbstract
A goal of neuroscience is to obtain a causal model of the nervous system. The recently reported whole-brain fly connectome 1–3 specifies the synaptic paths by which neurons can affect each other, but not how strongly they do affect each other in vivo. To overcome this limitation, we introduce a combined experimental and statistical strategy for efficiently learning a causal model of the fly brain, which we refer to as the ‘effectome’. Specifically, we propose an estimator for a linear dynamical model of the fly brain that uses stochastic optogenetic perturbation data to estimate causal effects and the connectome as a prior to greatly improve estimation efficiency. We validate our estimator in connectome-based linear simulations and show that it recovers a linear approximation to the nonlinear dynamics of more biophysically realistic simulations. We then analyse the connectome to propose circuits that dominate the dynamics of the fly nervous system. We discover that the dominant circuits involve only relatively small populations of neurons—thus, neuron-level imaging, stimulation and identification are feasible. This approach also re-discovers known circuits and generates testable hypotheses about their dynamics. Overall, we provide evidence that fly whole-brain dynamics are generated by a large collection of small circuits that operate largely independently of each other. This implies that a causal model of a brain can be feasibly obtained in the fly.
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This effort has now been extended to leverage the full connectome and to predict taste responses of neurons.
“This effort has now been extended to leverage the full connectome34,39 and to—for example—predict taste responses of neurons34.”
From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [39]
The Abstract and Discussion describe using the whole-brain fly connectome to guide a model of neural dynamics. They do not report predicting neurons’ taste responses: the examples concern visual circuits, and the Related connectomic work section describes predicting responses to novel sensory stimuli as a future direction. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredShiu et al. and Pospisil et al. use the connectome to model Drosophila brain dynamics and include connection weights and putative connection signs.
“Shiu et al.34 and Pospisil et al.39 use the connectome to model Drosophila brain dynamics and include connection weights (number of synapses) and putative connection signs (excitatory or inhibitory).”
From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [39]
The central complex and the mushroom body are notable exceptions to SEZ interactions, suggesting less crosstalk between those circuits and neurons in the SEZ.
“Notable exceptions are the central complex (ellipsoid body, fan-shaped body, protocerebral bridge and noduli) and the mushroom body, suggesting less crosstalk between those circuits and neurons in the SEZ (explored in more detail in Fig. 6; see also Pospisil et al.39).”
From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [39]
The ‘Global dynamics of putative effectome’ section describes anatomically localized circuits in the mushroom body and ellipsoid body, and the Discussion describes small circuits operating largely independently. Neither passage compares their interactions with SEZ neurons to those of other circuits. Searches for SEZ crosstalk and the named central-complex regions found no passage establishing the claimed exceptions. (LLM, conf=0.73)
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- Authors
- Pospisil, D. A., Aragon, M. J., Dorkenwald, S., Matsliah, A., Sterling, A. R., Schlegel, P., Yu, S.-C., McKellar, C. E., Costa, M., Eichler, K., Jefferis, G. S. X. E., Murthy, M., & Pillow, J. W.
- Affiliations
- Princeton University (US)
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- Corresponding author
- Pospisil, Dean A.
- Aragon, Max J.
- ORCID
- Venue
- Nature
- Published
- 2024-10-02
- Volume
- 634
- Issue
- 8032
- Pages
- 201-209
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC11446844
- OpenAlex
- W4403062933
- Cited by
- 36
- References
- 40
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 5
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (220343/Z/20/Z, 203261/Z/16/Z)
- National Institutes of Health (NS104899)
- Medical Research Council (MC-U105188491, U105188491, MC_EX_MR/T046279/1)
- National Institute of Mental Health (RF1MH117815, RF1MH129268)
- National Institute on Drug Abuse (RF1DA056404)
- National Institute of Neurological Disorders and Stroke (R01NS104899, NS104899, U24NS126935, R35NS111580)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Drosophila connectome, linear dynamical systems, causal effect estimation, neural circuits, whole-brain dynamics, nonlinear neural dynamics
- MeSH terms
- Animals, Brain, Drosophila melanogaster, Female, Male, Models, Neurological, Neural Pathways, Neurons, Stochastic Processes, Reproducibility of Results, Linear Models, Optogenetics, Connectome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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