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Briefing Document: Neuronal Wiring Diagram of an Adult Brain
Source: Dorkenwald, Sven, et al. "Neuronal Wiring Diagram of an Adult Brain." 2023.
Main Theme: This groundbreaking research paper details the complete connectome of an adult Drosophila melanogaster (fruit fly) brain, called "FlyWire." This marks a significant leap in connectomics, moving beyond partial reconstructions to a whole-brain wiring diagram.
Key Findings:
1. Connectome Completeness:
FlyWire encompasses 127,978 neurons and 53 million synapses, a substantial increase in scale compared to the previous "hemibrain" reconstruction and other connectomes like C. elegans.
This comprehensive map includes the subesophageal zone (SEZ), both optic lobes, and neurons extending through the nerves and neck connective, enabling researchers to trace sensorimotor pathways.
2. Centralized Brain Architecture:
Intrinsic neurons (neurons fully contained within the brain) constitute 75% of the adult fly nervous system and 84% of brain neurons, highlighting a high degree of brain centralization.
This signifies that the fly brain primarily communicates within itself and secondarily with the external world, contrasting with less centralized nervous systems like that of the larval fly or C. elegans.
3. Afferent and Efferent Pathways:
The researchers meticulously identified afferent (sensory) and efferent (motor/output) neurons, linking 95% of sensory neurons to their corresponding sensory organs.
Non-visual sensory inputs primarily target the antennal lobe (olfaction) and the SEZ (gustation and mechanosensation).
Efferent neurons, including motor and endocrine neurons, largely originate in the SEZ, emphasizing its role in integrating sensory information and driving behavior.
4. Visual Dominance:
The optic lobes house the majority of intrinsic neurons (73,655), underscoring the importance of vision for Drosophila.
The connectome reveals a highly organized visual system with columnar structures, tiling receptive fields, and distinct cell types exhibiting stereotypy across individuals and hemispheres.
5. Neuron Size and Connections:
Neuron size and shape are highly variable, with path lengths spanning two orders of magnitude.
The number of synapses a neuron forms correlates strongly with its path length and the number of connections it makes.
GABAergic and glutamatergic neurons (putative inhibitory neurons) tend to be larger and have higher degrees (number of connections) compared to cholinergic neurons.
6. Information Flow and Brain Regions:
The researchers used a probabilistic model to map information flow within the connectome, revealing how sensory information reaches different brain regions.
The SEZ interacts with most brain areas except the central complex and mushroom body.
Information from all sensory modalities eventually reaches all central brain neurons, demonstrating the interconnected nature of the fly brain.
7. Cell Type Annotations and Circuit Function:
Community efforts have yielded annotations for 59,548 neurons, categorizing them by cell type and function.
This classification, combined with the connectome, facilitates the generation of testable hypotheses about circuit function.
8. Ocellar Circuit Example:
FlyWire's completeness allows for tracing complete sensorimotor pathways, exemplified by the ocellar circuit.
The researchers identified specific descending neurons (DNs) that receive strong input from ocellar projection neurons, highlighting potential circuits for mediating flight control and orientation.
9. Future Directions:
FlyWire provides a foundation for integrating connectomics with other data modalities like transcriptomics, enabling a deeper understanding of brain development and function.
Further analysis of the connectome will uncover organizational principles, network motifs, and cell type-specific connectivity patterns.
This work paves the way for building computational models that simulate brain activity and predict behavior based on circuit structure.
Quotes of Note:
"The wiring diagram from our whole brain reconstruction is complete enough to deserve the name 'connectome.'"
"Intrinsic neurons of the brain make up three quarters of the adult fly nervous system, indicating a high degree of centralization in the brain."
"Given that the visual areas dominate the count, it seems safe to say that Drosophila is a highly visual animal."
"Clearly more fly connectomes at multiple developmental stages are needed."
Significance:
This study represents a monumental achievement in connectomics, providing an invaluable resource for neuroscience research. The availability of a complete adult Drosophila brain connectome opens up unprecedented opportunities to investigate the relationship between neuronal circuits, brain function, and behavior.
8 окт 2024
