A multi-scale brain map derived from whole-brain volumetric reconstructions

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment1. This organization relies on features across scales—from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain2. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved. Here we present a complete structure–function model of the main neuropil in the nematode Caenorhabditis elegans—the nerve ring—which we derive by integrating the volumetric reconstructions from two animals with corresponding3 synaptic and gap-junctional connectomes. Whereas previously the nerve ring was considered to be a densely packed tract of neural processes, we uncover internal organization and show how local neighbourhoods spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and identify a candidate reference connectome for the core circuit. Using this reference, we propose a modular network architecture of the C. elegans brain that supports sensory computation and integration, sensorimotor convergence and brain-wide coordination. These findings reveal scalable and robust features of brain organization that may be universal across phyla

Rotatable microfluidic device for simultaneous study of bilateral chemosensory neurons in Caenorhabditis elegans

The nematode Caenorhabditis elegans is a leading model system in genetics, development and neurobiology; its transparent body and small size make it particularly suitable for fluorescent imaging of cells and neurons within microfluidic setups. Simultaneously recording activity in bilaterally symmetric cells has proved difficult in C. elegans because the worm enters the chip and is then immobilised when it is lying on one side of the body. We developed a side-view rotatable microfluidic device that allows us to image a pair of bilateral neurons in a single focal plane of an epi-fluorescence microscope. We demonstrated the utility of the device by recording the responses of immobilised worms to controlled stimuli, focusing on the responses of two classes of head sensory neurons to changes in NaCl concentration. The results indicate that responses of ASE left and right and ASH left and right sensory neurons are stochastic. Simultaneous recordings of ASH left and right neurons tend to synchronise, pointing to a role of gap junctional connectivity. The anatomy of the C. elegans nerve ring makes this microfluidic approach ideally suited for the study of spatially extended pairs of neurons or larger neuronal circuits that lie within a limited depth of field