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Miller Lab

The neuropeptidergic connectome of C. elegans

AUTHORS

Ripoll-Sánchez LLidia , Watteyne JJan , Sun HHaoSheng , Fernandez RRobert , Taylor SRSeth R , Weinreb AAlexis , Bentley BLBarry L , Hammarlund MMarc , Miller DMDavid M , Hobert OOliver , Beets IIsabel , Vértes PEPetra E , Schafer WRWilliam R . Neuron. 2023 11 6; 111(22). 3570-3589.e5

ABSTRACT

Efforts are ongoing to map synaptic wiring diagrams, or connectomes, to understand the neural basis of brain function. However, chemical synapses represent only one type of functionally important neuronal connection; in particular, extrasynaptic, “wireless” signaling by neuropeptides is widespread and plays essential roles in all nervous systems. By integrating single-cell anatomical and gene-expression datasets with biochemical analysis of receptor-ligand interactions, we have generated a draft connectome of neuropeptide signaling in the C. elegans nervous system. This network is characterized by high connection density, extended signaling cascades, autocrine foci, and a decentralized topology, with a large, highly interconnected core containing three constituent communities sharing similar patterns of input connectivity. Intriguingly, several key network hubs are little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate that the C. elegans neuropeptidergic connectome will serve as a prototype to understand how networks of neuromodulatory signaling are organized.