Synthetic ablations in the C. elegans nervous system

Abstract

Synthetic lethality, the finding that the simultaneous knockout of two or more individually non-essential genes leads to cell or organism death, has offered a systematic framework to explore cellular function, and also offered therapeutic applications. Yet, the concept lacks its parallel in neuroscience - a systematic knowledge base on the role of double or higher order ablations in the functioning of a neural system. Here, we use the framework of network control to systematically predict the ablation of neuron pairs and triplets. We find that surprisingly small sets of 58 pairs and 46 triplets can reduce muscle controllability, and that these sets are localised in the nervous system in distinct groups. Further, they lead to highly specific experimentally testable predictions about mechanisms of loss of control, and which muscle cells are expected to experience this loss.