FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system

Abstract

Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode can adapt to harsh environments by undergoing a whole-animal change, involving exiting reproductive development and entering the stress-resistant dauer larval stage. The dauer is a dispersal stage with dauer-specific behaviors for finding and stowing onto carrier animals, but how dauers acquire these behaviors, despite having a physically limited nervous system of 302 neurons, is poorly understood. We compared dauer and reproductive development using whole-animal RNA sequencing at fine time points and at sufficient depth to measure transcriptional changes within single cells. We detected 8,042 genes differentially expressed during dauer and reproductive development and observed striking up-regulation of neuropeptide genes during dauer entry. We knocked down neuropeptide processing using mutants and demonstrate that neuropeptide signaling promotes the decision to enter dauer rather than reproductive development. We also demonstrate that during dauer neuropeptides modulate the dauer-specific nictation behavior (carrier animal-hitchhiking) and are necessary for switching from repulsion to CO (a carrier animal cue) in nondauers to CO attraction in dauers. We tested individual neuropeptides using CRISPR knockouts and existing strains and demonstrate that the combined effects of and mimic the effects of on nictation and CO attraction. Through meta-analysis, we discovered similar up-regulation of neuropeptides in the dauer-like infective juveniles of diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT-1. Our findings reveal that, under stress, increased neuropeptide signaling in enhances their decision-making accuracy and expands their behavioral repertoire.

Lineage context switches the function of aC. elegansPax6 homolog in determining a neuronal fate

“…Under normal cultivation conditions, activation of BAG neurons by hypoxia or CO 2 triggers an acute avoidance response and negative chemotaxis, indicating that environments with high CO 2 or low oxygen are aversive to C. elegans. BAGmediated avoidance behavior requires that BAG neurons release the neurotransmitter glutamate and neuropeptides (Lee et al, 2017;Guillermin et al, 2017;Hallem and Sternberg, 2008). These neurochemical signals act on interneurons of the RIA, RIG, AIY and AIZ types, some of which receive direct synaptic inputs from BAGs and all of which are required for CO 2 chemotaxis (Guillermin et al, 2017).…”

The Regulation of Developmental Diapause is Coordinated with Molting and Olfaction

“…To achieve organismal plasticity, it is has been shown that C. elegans dauer 580 entry involves the remodeling of glia and neural circuitry, as well as differential 581 expression of chemosensory and neuropeptide receptors [3,4,6,7,19]. While 582 dauer-induced remodeling of the AWC dendritic ends that increase their surface 583 area could heighten sensitivity, our results show that wild-type, daf-2, and daf-7 584 DL were actually less attracted than adults to several odors, and the DL of two daf-585 7 alleles even displayed avoidance of isoamyl alcohol.…”

“…In C. elegans adults, the AWA neurons detect 2,3-butanedione 591 (diacetyl), while the AWC neurons sense isoamyl alcohol and 2,3-pentanedione. 592 A significant upregulation of neuropeptide expression during dauer entry occurs in 593 both C. elegans and P. pacificus [86], some of which may correlate with stage-594 specific olfactory behavior, as well as dauer-specific behaviors such as nictation 595 and the change in CO2 response valence [6]. A combination of cellular identity and 596 gene expression changes may be responsible for stage-specific chemosensory 597 behaviors between adults and DL [69,70].…”

“…Caenorhabditis elegans, as well as the equivalent infective juvenile (IJ) or infective 42 third-larval (iL3) stages in parasitic nematodes, undergo spectacular physiological, 43 morphological and neuroanatomical changes [3][4][5]. At the gene expression level, 44 a number of the dauer entry changes are reversible while some become 45 permanent life history traits that mark dauer passage [6,7]. Entry into the dauer 46 stage is primarily determined by environmental factors, particularly the depletion 47 of food, elevated temperature, and high levels of ascaroside dauer pheromones in example of developmental plasticity that is becoming more amenable to genetic 51 Results 142 P. pacificus Daf-c mutants have an exsheathment phenotype 143 P. pacificus dauer larvae (DL) can be induced by starvation, crowding, or high 144 temperature (≥25ºC).…”

“…For both parasitic and free-living nematodes, 68 DL share the ability to survive harsh conditions but remain receptive to 69 semiochemicals from their environment. 70The commitment to dauer also prompts the rewiring of the sensory nervous 71 system in C. elegans [6,18,19], but the molecular basis of this process remains 72 poorly understood [20]. Comparisons of chemosensory behaviors in reproductive 73 free-living adults versus developmentally arrested DL or iL3s have revealed that 74 responses to some chemosensory cues change dramatically across life stages.…”