Dvali, S. | bioRxiv Science

bioRxiv2025

Hierarchical Community Structure of the Adult Drosophila Connectome Reveals Conserved Circuit Archetypes

The community structure of connectomes supports functional specialization, adaptability, and cost-efficient wiring. However, little is known about communities in connectomes mapped at the level of individual neurons and synapses. Here, we analyze a whole-brain Drosophila adult connectome using a nested stochastic blockmodel to uncover its hierarchical community structure. Most of the roughly 1500 fine-scale communities-the smallest, and best resolved level of the hierarchy- are spatially compact, mostly assortative, and aligned with biological features. Nonetheless, we find evidence of nonassortative communities, spatially co-localized within the optic lobe and vision-processing pathways. Seeking "functional primitives"-small circuits with functionally narrow feature profiles-we use data-driven clustering to group communities into 45 archetypical meta-clusters based on their spatial, functional, and molecular properties, revealing modular building blocks from which larger, functionally diverse communities are composed. This work advances our understanding of how structure and function are organized in the fruit fly brain and highlights the value of statistical network models in interpreting nanoscale connectomes.

neuroscience↗

bioRxiv2023

TWISP: A Transgenic Worm for Interrogating Signal Propagation in C. elegans

Genetically encoded optical indicators and actuators of neural activity allow for all-optical investigations of signaling in the nervous system. But commonly used indicators, actuators and expression strategies are poorly suited for systematic measurements of signal propagation at brain scale and cellular resolution. Large scale measurements of the brain require indicators and actuators with compatible excitation spectra to avoid optical crosstalk. They must be highly expressed in every neuron but at the same time avoid lethality and permit the animal to reach adulthood. And finally, their expression must be compatible with additional fluorescent labels to locate and identify neurons, such as those in the NeuroPAL cell identification system. We present TWISP, a Transgenic Worm for Interrogating Signal Propagation, that address these needs and enables optical measurements of evoked calcium activity at brain scale and cellular resolution in the nervous system of the nematode Caenorhabditis elegans. We express in every neuron a non-conventional optical actuator, the gustatory receptor homolog GUR-3+PRDX-2 under the control of a drug-inducible system QF+hGR, and calcium indicator GCAMP6s, in a background with additional fluorophores of the NeuroPAL cell ID system. We show that this combination, but not others tested, avoids optical-crosstalk, creates strong expression in the adult, and generates stable transgenic lines for systematic measurements of signal propagation in the worm brain.

neuroscience↗