An entropic measure of diverse specialization highlights multifunctional neurons in annotated connectomes

Netw Neurosci. 2026 Mar 20;10(1):204-220. doi: 10.1162/NETN.a.533. eCollection 2026.

Abstract

The creation and curation of synaptic-level neuronal networks, or connectomes, enables the study of the relationship between neuronal structure and function. Topological characteristics of neuronal networks have been studied extensively. Separately, there have been considerable efforts to classify the morphology, cell types, and lineages of neurons. Here, we introduce a network metric that combines topological analysis with node metadata. This entropic quantity measures the diversity of incoming or outgoing connections to a node in terms of the metadata distribution. We find that in Caenorhabditis elegans, the top-scoring neurons (PVR, RMGL/R, DVA, CEP, ADE, URXR, RIGL, BAG, SMBDL) have known functions that integrate and disseminate multimodal information involved in sensorimotor functions. In the nerve cord of Drosophila melanogaster, we find that top-scoring neurons are embryonic neurons located in the abdominal neuropil, where sensorimotor coordination is required for complex innate behavior such as mating.

Keywords: Annotated networks; C. Elegans; Connectome; Drosophila melanogaster; Entropy; Information flow.

Plain language summary

Most brain network data sets are endowed with a catalogue of annotations that supplement the anatomical connectivity. Annotations grant additional interpretability in conjunction with network analysis, and methodology incorporating metadata have been understudied. We introduce a measure based on information entropy to quantify a given neuron’s level of diverse specialisms of its partners. Here, we consider anatomical and developmental annotations for the C. elegans and the Drosophila nerve cord connectomes. Our results verify prior experimental findings in identifying neurons that integrate and disseminate specialized channels of annotation connectivity.