Pathogenic bacteria modulate pheromone response to promote mating.

Pathogens generate ubiquitous selective pressures and host-pathogen interactions alter social behaviours in many animals1-4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal5-13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.

Forgetting generates a novel state that is reactivatable.

Forgetting is defined as a time-dependent decline of a memory. However, it is not clear whether forgetting reverses the learning process to return the brain to the naive state. Here, using the aversive olfactory learning of pathogenic bacteria in C. elegans, we show that forgetting generates a novel state of the nervous system that is distinct from the naive state or the learned state. A transient exposure to the training condition or training odorants reactivates this novel state to elicit the previously learned behavior. An AMPA receptor and a type II serotonin receptor act in the central neuron of the learning circuit to decrease and increase the speed to reach this novel state, respectively. Together, our study systematically characterizes forgetting and uncovers conserved mechanisms underlying the rate of forgetting.

Redundant neural circuits regulate olfactory integration.

Olfactory integration is important for survival in a natural habitat. However, how the nervous system processes signals of two odorants present simultaneously to generate a coherent behavioral response is poorly understood. Here, we characterize circuit basis for a form of olfactory integration in Caenorhabditis elegans. We find that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly blocks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde, that signal food. Using a forward genetic screen, we found that genes known to regulate the structure and function of sensory neurons, osm-5 and osm-1, played a critical role in the integration process. Loss of these genes mildly reduces the response to the repellent 2-nonanone and disrupts the integration effect. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue. Sensory neurons AWB and downstream interneurons AVA, AIB, RIM that play critical roles in olfactory sensorimotor response are able to process signals generated by 2-nonanone or IAA or the mixture of the two odorants and contribute to the integration. Thus, our results identify redundant neural circuits that regulate the robust effect of a repulsive odorant to block responses to attractive odorants and uncover the neuronal and cellular basis for this complex olfactory task.

Pheromones Modulate Learning by Regulating the Balanced Signals of Two Insulin-like Peptides.

Social environment modulates learning through unknown mechanisms. Here, we report that a pheromone mixture that signals overcrowding inhibits C. elegans from learning to avoid pathogenic bacteria. We find that learning depends on the balanced signaling of two insulin-like peptides (ILPs), INS-16 and INS-4, which act respectively in the pheromone-sensing neuron ADL and the bacteria-sensing neuron AWA. Pheromone exposure inhibits learning by disrupting this balance: it activates ADL and increases expression of ins-16, and this cellular effect reduces AWA activity and AWA-expressed ins-4. The activities of the sensory neurons are required for learning and the expression of the ILPs. Interestingly, pheromones also promote the ingestion of pathogenic bacteria while increasing resistance to the pathogen. Thus, the balance of the ILP signals integrates social information into the learning process as part of a coordinated adaptive response that allows consumption of harmful food during times of high population density.

WIP-1 and DBN-1 promote scission of endocytic vesicles by bridging actin and Dynamin-1 in the C. elegans intestine.

There has been a consensus that actin plays an important role in scission of the clathrin-coated pits (CCPs) together with large GTPases of the dynamin family in metazoan cells. However, the recruitment, regulation and functional interdependence of actin and dynamin during this process remain inadequately understood. Here, based on small-scale screening and in vivo live-imaging techniques, we identified a novel set of molecules underlying CCP scission in the multicellular organism Caenorhabditis elegans We found that loss of Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP-1) impaired CCP scission in a manner that is independent of the C. elegans homolog of WASP/N-WASP (WSP-1) and is mediated by direct binding to G-actin. Moreover, the cortactin-binding domain of WIP-1 serves as the binding interface for DBN-1 (also known in other organisms as Abp1), another actin-binding protein. We demonstrate that the interaction between DBN-1 and F-actin is essential for Dynamin-1 (DYN-1) recruitment at endocytic sites. In addition, the recycling regulator RME-1, a homolog of mammalian Eps15 homology (EH) domain-containing proteins, is increasingly recruited at the arrested endocytic intermediates induced by F-actin loss or DYN-1 inactivation, which further stabilizes the tubular endocytic intermediates. Our study provides new insights into the molecular network underlying F-actin participation in the scission of CCPs.This article has an associated First Person interview with the first author of the paper.

Cholinergic Sensorimotor Integration Regulates Olfactory Steering.

Sensorimotor integration regulates goal-directed movements. We study the signaling mechanisms underlying sensorimotor integration in C. elegans during olfactory steering, when the sinusoidal movements of the worm generate an in-phase oscillation in the concentration of the sampled odorant. We show that cholinergic neurotransmission encodes the oscillatory sensory response and the motor state of head undulations by acting through an acetylcholine-gated channel and a muscarinic acetylcholine receptor, respectively. These signals converge on two axonal domains of an interneuron RIA, where the sensory-evoked signal suppresses the motor-encoding signal to transform the spatial information of the odorant into the asymmetry between the axonal activities. The asymmetric synaptic outputs of the RIA axonal domains generate a directional bias in the locomotory trajectory. Experience alters the sensorimotor integration to generate specific behavioral changes. Our study reveals how cholinergic neurotransmission, which can represent sensory and motor information in the mammalian brain, regulates sensorimotor integration during goal-directed locomotions.