Of what use is connectomics? A personal perspective on the Drosophila connectome
Abstract
The brain is a network of neurons and its biological output is behaviour. This is an exciting age, with a growing acknowledgement that the comprehensive compilation of synaptic circuits densely reconstructed in the brains of model species is now both technologically feasible and a scientifically enabling possibility in neurobiology, much as 30 years ago genomics was in molecular biology and genetics. Implemented by huge advances in electron microscope technology, especially focused ion beam-scanning electron microscope (FIB-SEM) milling (see Glossary), image capture and alignment, and computer-aided reconstruction of neuron morphologies, enormous progress has been made in the last decade in the detailed knowledge of the actual synaptic circuits formed by real neurons, in various brain regions of the fly Drosophila. It is useful to distinguish synaptic pathways that are major, with 100 or more presynaptic contacts, from those that are minor, with fewer than about 10; most neurites are both presynaptic and postsynaptic, and all synaptic sites have multiple postsynaptic dendrites. Work on Drosophila has spearheaded these advances because cell numbers are manageable, and neuron classes are morphologically discrete and genetically identifiable, many confirmed by reporters. Recent advances are destined within the next few years to reveal the complete connectome in an adult fly, paralleling advances in the larval brain that offer the same prospect possibly within an even shorter time frame. The final amendment and validation of segmented bodies by human proof-readers remains the most time-consuming step, however. The value of a complete connectome in Drosophila is that, by targeting to specific neurons transgenes that either silence or activate morphologically identified circuits, and then identifying the resulting behavioural outcome, we can determine the causal mechanism for behaviour from its loss or gain. More importantly, the connectome reveals hitherto unsuspected pathways, leading us to seek novel behaviours for these. Circuit information will eventually be required to understand how differences between brains underlie differences in behaviour, and especially to herald yet more advanced connectomic strategies for the vertebrate brain, with an eventual prospect of understanding cognitive disorders having a connectomic basis. Connectomes also help us to identify common synaptic circuits in different species and thus to reveal an evolutionary progression in candidate pathways.
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In general, a mixture of presynapses and postsynapses is found on all non-primary neurites.
“However, in general, a mixture of presynapses and postsynapses is found on all non-primary neurites10,33,53,65 (Fig. 3b).”
From Neuronal wiring diagram of an adult brain (2024) · cites this paper as [65]
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- Authors
- Meinertzhagen, I. A.
- Affiliations
- Dalhousie University (CA)
- Corresponding author
- Meinertzhagen, Ian A.
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2018-05-15
- Volume
- 221
- Issue
- 10
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- OpenAlex
- W2810250526
- Cited by
- 53
- References
- 11
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 6 · 2018: 4
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Experimental Biology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- connectomics, Drosophila connectome, synaptic circuits, FIB-SEM, larval brain, brain evolution, cognitive disorders, comparative neuroanatomy
- MeSH terms
- Animals, Behavior, Animal, Brain, Drosophila melanogaster, Larva, Neurons, Connectome
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