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.