Impairing one sensory modality enhances another by reconfiguring peptidergic signalling 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. We probe such mechanisms by performing a forward genetic screen for mutants with enhanced O 2 perception in Caenorhabditis elegans . Multiple mutants exhibiting increased O 2 responsiveness 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 pheromone-sensing neurons. At the same time, ADL responsiveness to pre-synaptic input from O 2 -sensing neurons is heightened in qui-1 , and other sensory defective mutants, resulting in enhanced neurosecretion although not increased Ca 2+ responses. Expressing qui-1 selectively in ADL rescues both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O 2 . Profiling ADL neurons in qui-1 mutants highlights extensive changes in gene expression, notably of many neuropeptide receptors. We show that elevated ADL expression of the conserved neuropeptide receptor NPR-22 is necessary for enhanced ADL neurosecretion in qui-1 mutants, and is sufficient to confer increased ADL neurosecretion in control animals. Sensory loss can thus confer cross-modal plasticity by changing the peptidergic connectome.