The First Connectome of a Complex Ventral Nerve Cord

by Griffin Badalamente

As recently announced, the Drosophila Connectomics group has preprinted three new papers documenting the creation, characterisation, and analysis of the complete connectome of a ventral nerve cord (VNC) of an adult male Drosophila melanogaster. The VNC is the insect equivalent of the vertebrate spinal cord and includes axons of descending neurons relaying instructions from the brain and of sensory neurons that carry information from the periphery, as well as motor neurons that activate muscles for flying, walking, and mating. The lab worked with the FlyEM project team at Janelia Research Campus and other collaborators in the US and UK to carefully reconstruct and describe more than 23,000 neurons at synaptic resolution, contextualising this highly detailed network based on decades of experimental work.

The first of the three papers, A Connectome of the Male Drosophila Ventral Nerve Cord, by S. Takemura et al., describes the methods by which the VNC EM volume was prepared, imaged, and assembled for automated reconstruction in collaboration with Google, followed by manual editing and reconstruction by Janelia and Cambridge proofreaders.

A selection of reconstructed neurons. The neurons shown here comprise 4% of all reconstructed neurons in the VNC. (Figure 2 from Takemura et al., 2023)

The second paper, Systematic annotation of a complete adult male Drosophila nerve cord connectome reveals principles of functional organisation, by E.C. Marin et al. is primarily an atlas that describes the features we annotated and used to assign cell types but includes preliminary analysis of network properties. Neurons are generated by segmentally repeating arrays of neural stem cells, resulting in, for example, the same cell types working together to control the pairs of legs in each of the three thoracic segments. The daughters produced by each neural stem cell are diverse but tend to display broadly similar morphology and connectivity and to express the same fast-acting neurotransmitter. For the first time, we were able to evaluate the validity of the network predicted by earlier studies based on immature populations of neurons at an earlier developmental stage.

Circuit diagram describing strong interactions between neural stem cell progeny in the VNC. (Figure 56B from Marin et al., 2023).

The third paper, Transforming descending input into behavior: The organization of premotor circuits in the Drosophila Male Adult Nerve Cord connectome, by H.S.J. Cheong, K. Eichler, and T. Stürner, et al., describes how premotor circuits in the VNC are structured, both locally and in the context of the whole fly nervous system. From our group, Katharina Eichler and Tomke Stürner painstakingly matched light-level images to individual neurons in the dataset to reconstruct specific leg motor control circuits in the connectome. Identifying descending neurons that allow the brain to communicate with the VNC allowed us not just to analyse local circuits, but also to put them in the context of information flow in the central nervous system. This level of detail means we can reconstruct a standard leg circuit at synapse level precision.