Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in <i>Caenorhabditis elegans</i>.

Abstract

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 O₂ perception in <i>Caenorhabditis elegans</i>. Multiple mutants exhibiting increased O₂ responsiveness concomitantly show defects in other sensory responses. One mutant, <i>qui-1</i>, defective in a conserved NACHT/WD40 protein, abolishes pheromone-evoked Ca²⁺ responses in the ADL pheromone-sensing neurons. At the same time, ADL responsiveness to pre-synaptic input from O₂-sensing neurons is heightened in <i>qui-1</i>, and other sensory defective mutants, resulting in enhanced neurosecretion although not increased Ca²⁺ responses. Expressing <i>qui-1</i> selectively in ADL rescues both the <i>qui-1</i> ADL neurosecretory phenotype and enhanced escape from 21% O₂. Profiling ADL neurons in <i>qui-1</i> 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 <i>qui-1</i> 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.