Hierarchical Modular Structure of theDrosophilaConnectome
Authors: Kunin Alexander B. , Guo Jiahao , Bassler Kevin E. , Pitkow Xaq , Josić Krešimir 
Published: August 2023

The structure of neural circuitry plays a crucial role in brain function. Previous studies of brain organization generally had to trade off between coarse descriptions at a large scale and fine descriptions on a small scale. Researchers have now reconstructed tens to hundreds of thousands of neurons at synaptic resolution, enabling investigations into the interplay between global, modular organization, and cell type-specific wiring. Analyzing data of this scale, however, presents unique challenges. To address this problem, we applied novel community detection methods to analyze the synapse-level reconstruction of an adult femaleDrosophila melanogasterbrain containing >20,000 neurons and 10 million synapses. Using a machine-learning algorithm, we find the most densely connected communities of neurons by maximizing a generalized modularity density measure. We resolve the community structure at a range of scales, from large (on the order of thousands of neurons) to small (on the order of tens of neurons). We find that the network is organized hierarchically, and larger-scale communities are composed of smaller-scale structures. Our methods identify well-known features of the fly brain, including its sensory pathways. Moreover, focusing on specific brain regions, we are able to identify subnetworks with distinct connectivity types. For example, manual efforts have identified layered structures in the fan-shaped body. Our methods not only automatically recover this layered structure, but also resolve finer connectivity patterns to downstream and upstream areas. We also find a novel modular organization of the superior neuropil, with distinct clusters of upstream and downstream brain regions dividing the neuropil into several pathways. These methods show that the fine-scale, local network reconstruction made possible by modern experimental methods are sufficiently detailed to identify the organization of the brain across scales, and enable novel predictions about the structure and function of its parts.

Significance StatementThe Hemibrain is a partial connectome of an adult femaleDrosophila melanogasterbrain containing >20,000 neurons and 10 million synapses. Analyzing the structure of a network of this size requires novel and efficient computational tools. We applied a new community detection method to automatically uncover the modular structure in the Hemibrain dataset by maximizing a generalized modularity measure. This allowed us to resolve the community structure of the fly hemibrain at a range of spatial scales revealing a hierarchical organization of the network, where larger-scale modules are composed of smaller-scale structures. The method also allowed us to identify subnetworks with distinct cell and connectivity structures, such as the layered structures in the fan-shaped body, and the modular organization of the superior neuropil. Thus, network analysis methods can be adopted to the connectomes being reconstructed using modern experimental methods to reveal the organization of the brain across scales. This supports the view that such connectomes will allow us to uncover the organizational structure of the brain, which can ultimately lead to a better understanding of its function.