Impairing one sensory modality enhances another by reprogramming peptidergic circuits in Caenorhabditis elegans

Animals that lose one sensory modality often show augmented responses to other sensory inputs. The mechanisms underpinning this cross-modal plasticity are poorly understood. To probe these mechanisms, we perform a forward genetic screen for mutants with enhanced O ₂ perception in C. elegans . Multiple mutants exhibiting increased responsiveness to O ₂ concomitantly show defects in other sensory responses. One mutant, qui-1 , defective in a conserved NACHT/WD40 protein, abolishes pheromone-evoked Ca ²⁺ responses in the ADL chemosensory neurons. We find that ADL’s responsiveness to pre-synaptic input from O ₂ - sensing neurons is heightened in qui-1 and other sensory defective mutants resulting in an enhanced neurosecretion. Expressing qui-1 selectively in ADL rescues both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O ₂ . Profiling of ADL neurons indicates its acquired O ₂ -evoked neurosecretion is the result of a transcriptional reprogramming that up-regulates neuropeptide signalling. We show that the conserved neuropeptide receptor NPR-22 is necessary and sufficient in ADL to enhance its neurosecretion levels. Sensory loss can thus confer cross-modal plasticity by re-wiring peptidergic circuits.