Search

Caenorhabditis elegans expresses human Werner syndrome protein (WRN) orthologs as two distinct proteins: MUT-7, with a 3′−5′ exonuclease domain, and CeWRN-1, with helicase domains. How these domains cooperate remains unclear. Here, we demonstrate the different contributions of MUT-7 and CeWRN-1 to 22G small interfering RNA (siRNA) synthesis and the plasticity of neuronal signaling. MUT-7 acts specifically in the cytoplasm to promote siRNA biogenesis and in the nucleus to associate with CeWRN-1. The import of siRNA by the nuclear Argonaute NRDE-3 promotes the loading of the heterochromatin-binding protein HP1 homolog HPL-2 onto specific loci. This heterochromatin complex represses the gene expression of the guanylyl cyclase ODR-1 to direct olfactory plasticity in C. elegans. Our findings suggest that the exonuclease and helicase domains of human WRN may act in concert to promote RNA-dependent loading into a heterochromatin complex, and the failure of this entire process reduces plasticity in postmitotic neurons.

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.

Sensory experience modifies behavior through both associative and non-associative learning. In Caenorhabditis elegans, pairing odor with food deprivation results in aversive olfactory learning, and pairing odor with food results in appetitive learning. Aversive learning requires nuclear translocation of the cGMP-dependent protein kinase EGL-4 in AWC olfactory neurons and an insulin signal from AIA interneurons. Here we show that the activity of neurons including AIA is acutely required during aversive, but not appetitive, learning. The AIA circuit and AGE-1, an insulin-regulated PI3 kinase, signal to AWC to drive nuclear enrichment of EGL-4 during conditioning. Odor exposure shifts the AWC dynamic range to higher odor concentrations regardless of food pairing or the AIA circuit, whereas AWC coupling to motor circuits is oppositely regulated by aversive and appetitive learning. These results suggest that non-associative sensory adaptation in AWC encodes odor history, while associative behavioral preference is encoded by altered AWC synaptic activity. DOI: http://dx.doi.org/10.7554/eLife.14000.001, eLife digest We learn from experience. When we repeatedly encounter a signal that is coupled to either reward or punishment, we eventually learn to expect the two to occur together. This phenomenon is called associative learning. Within the brain, distinct groups of neurons process information about the signal and about reward and punishment. In addition to storing information individually (as non-associative memories), the neurons communicate with one another and combine their information to create associations. Like humans and many other animals, the roundworm and model organism Caenorhabditis elegans can learn to associate odors with rewards or punishments. By teaching worms that a scent predicts either food or a lack of food, Cho et al. now show that different cells and molecules support the formation of these two associations. C. elegans detect odors using sensory neurons. Repeated exposure to an odor reduces a neuron’s sensitivity to that odor, and Cho et al. show that this occurs irrespective of whether the odor is paired with reward or with punishment. This indicates that the neuron stores information about the odor as a non-associative memory. By contrast, pairing an odor with reward has differing effects on associative learning to pairing that same odor with punishment. Pairing an odor with a reward increases a sensory neuron’s ability to communicate with target neurons – ultimately, those that control movement – whereas odor-punishment pairing reduces this ability. Further experiments showed that an insulin peptide supports learning about odors and punishments, but not about odors and rewards. The next challenge is to identify the molecules that strengthen or weaken communication between sensory neurons and target neurons after associative learning. It will also be important to identify the other neurons and molecules that detect rewards and punishments, to gain a more complete picture of how the brain acquires this information. DOI: http://dx.doi.org/10.7554/eLife.14000.002