Neuron-Microenvironments Associated with Specific Long-Range Connectivity Reveal Functional Modules in the Adult Drosophila Brain

Advances in electron microscopy (EM) and computational neuroscience enable large-scale neuronal reconstruction, yet existing methods often overlook surrounding neurons influence. Using a whole-brain EM dataset of Drosophila, we analyzed 50 million synapses and derived microenvironmental (MicroEnv) features for over 130,000 neurons categorized by polarity. This refined 78 brain regions into 482 subregions, forming a high-resolution MicroEnv-atlas. MicroEnv features improved spatial coherence by 68% compared to single-neuron morphological features and correlated with long-range projections in the Mushroom Body. Integration with scRNA-seq data revealed associations with transmembrane transport and metabolism, suggesting roles in intercellular communication. Clustering based on distal projections identified submodules aligned with functional hierarchies, including feeding and multisensory processing. Our framework highlights the value of microenvironmental context in mapping brain organization.