Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans

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 Caenorhabditis elegans. Multiple mutants exhibiting increased O2 responsiveness concomitantly show defects in other sensory responses. One mutant, qui-1, 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 qui-1, and other sensory defective mutants, resulting in enhanced neurosecretion although not increased Ca2+ responses. Expressing qui-1 selectively in ADL rescues both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O2. 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.

Glia detect and mount a protective response to loss of dendrite substructure integrity inC. elegans

“…15 To determine whether the glial response to cilia defects can also follow acute cilia perturbation, we designed an inducible cilia degradation system. Briefly, sequences encoding AID, an a uxin-inducible d egron, 30,31 were introduced into the genomic osm-6 locus of animals also ubiquitously expressing the AID-targeting scaffold protein TIR1 ( eft-3pro::TIR1-mRuby ; Figure 2A ; a related method is described in 32 ). While control animals carrying either osm-6::AID or eft-3pro::TIR1-mRuby , have no dye-filling defects, we found that in the majority of animals carrying both constructs, sensory neurons become dye-filling defective within 1.5 hours of auxin exposure ( Figure 2B ).…”

“…15 To determine whether the glial response to cilia defects can also follow acute cilia perturbation, we designed an inducible cilia degradation system. Briefly, sequences encoding AID, an auxin-inducible degron, 30,31 were introduced into the genomic osm-6 locus of animals also ubiquitously expressing the AID-targeting scaffold protein TIR1 (eft-3pro::TIR1-mRuby; Figure 2A; a related method is described in 32 ).…”

Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans

“…LURY-1 peptides are cognate ligands of the luqin-like receptor NPR-22/LUQR-1 and are the most potent ligands of this receptor in vitro ( Beets et al, 2023 ; Gadenne et al, 2022 ; Mertens et al, 2006 ; Ohno et al, 2017 ). Initially, LUQR-1 was described as a tachykinin-like receptor with roles in fat metabolism, sleep promotion, and control of neurosecretion in ADL neurons ( Keating et al, 2003 ; Palamiuc et al, 2017 ; Turek et al, 2016 ; Valperga and de Bono, 2022 ). Further phylogenetic analysis established LUQR-1 as an ortholog of the luqin/RYamide receptor family ancestral to bilaterian animals ( Beets et al, 2023 ; Jékely, 2013 ; Mirabeau and Joly, 2013 ; Ohno et al, 2017 ).…”

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity

“…Genes in the “Signal transduction” category were filtered by the gene ontology term “signal transduction” – GO:0007165. The categories “Transcription factors” and “Neuropeptides” were derived from a curated list of C. elegans transcription factors and neuronal genes (Hobert, 2013; Valperga and de Bono, 2022).…”

“… C) Enriched neuronal gene classes from temperature-dependent genes in AFD and whole animal samples using clusterProfiler (Yu et al, 2012) on curated C. elegans neuronal genes (Hobert, 2013; Valperga and de Bono, 2022). …”