Nematode mind: exploring the role of the RNA interference pathway in learning, memory and beyond

Abstract

Caenorhabditis nematodes, particularly the well-known Caenorhabditis elegans, have challenged early views of them as hard-wired by demonstrating diverse learning and memory capabilities. This cognitive repertoire, developed with just several hundred neurons, highlights the evolutionary importance of cognitive traits. In this study, we examine the relationship between learning, development, reproduction and lifespan, focusing on its regulation by the conserved RNA interference (RNAi) pathway. Specifically, we examine NRDE-3, a key Argonaute protein in this pathway using an RNAi-defective nrde-3 mutant to evaluate the effects of this mutation under two diets. Consistent with previous findings, nrde-3 mutants exhibited a trend towards deteriorated aversive learning; at the same time, no decline in positive learning was observed. Additionally, we found that the nrde-3 mutant had faster development but also reduced lifespan under the stressful condition of light exposure. We propose that the RNAi pathway, alongside the target of rapamycin and insulin/insulin-like signalling pathways, contributes to the correlated evolution of learning and life-history traits. Notably, recent research has linked the RNAi pathway to the epigenetic inheritance of learned behaviours, presenting new opportunities for integrated investigations into within-generation learning and transgenerational responses. Accordingly, we suggest future research directions that take advantage of the genomic resources, biodiversity and experimental tractability of Caenorhabditis.This article is part of the Theo Murphy meeting issue 'Selection shapes diverse animal minds'.

Keywords: Caenorhabditis elegans; NRDE-3 Argonaute protein; RNA interference (RNAi); learning and memory; life-history evolution.

Figure 1.

Schematic of the chemotaxis assay plate.

Figure 2.

Effects of nrde-3 mutation on learning. Opaque colours represent naïve, while transparent colours represent trained worms. Bars represent the chemotaxis index of strains of the indicated group (mean ± s.e.). (A) Aversive learning assay. (B) Appetitive learning assay.

Figure 3.

Effects of nrde-3 mutation on development time. Development time expressed as a proportion of developed worms calculated as mature/total in each plate. Three different time points were used. (A) Proportion of mature E. coli OP50 fed worms. (B) Proportion of mature E. coli HT115 (L4440) fed worms.

Figure 4.

Effects of nrde-3 mutation on reproduction. (A) Lifetime reproductive success of E. coli OP50 fed worms, reproduction mean points with ±s.e. bars. (B) Lifetime reproductive success of E. coli HT115 (L4440) fed worms, reproduction mean points with ±s.e. bars. (C) Individual fitness (λ_ind) calculated using the Euler–Lotka equation for E. coli OP50 fed worms, median with 95% confidence intervals is displayed. (D) Individual fitness (λ_ind) calculated using the Euler–Lotka equation for E. coli HT115 (L4440) fed worms, median with 95% confidence intervals is displayed.

Figure 5.

Impact of nrde-3 mutation on lifespan, represented by survival probability. In both cases, there was light during incubation (8 L : 16 D) as a late-life stressor. (A) Survival probability when feeding on E. coli OP50. (B) Survival probability when feeding on E. coli HT115 (L4440).