Learning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of C. elegans gustatory aversive learning. The NMU homolog CAPA-1 and its receptor NMUR-1 are required for the retrieval of learned salt avoidance. Gustatory aversive learning requires the release of CAPA-1 neuropeptides from sensory ASG neurons that respond to salt stimuli in an experience-dependent manner. Optogenetic silencing of CAPA-1 neurons blocks the expression, but not the acquisition, of learned salt avoidance. CAPA-1 signals through NMUR-1 in AFD sensory neurons to modulate two navigational strategies for salt chemotaxis. Aversive conditioning thus recruits NMU signaling to modulate locomotor programs for expressing learned avoidance behavior. Because NMU signaling is conserved across bilaterian animals, our findings incite further research into its function in other learning circuits.

Many challenges in biosensing originate from the fact that the all-important nanoarchitecture of the biosensor surface, including precise density and orientation of bioreceptors, is not entirely comprehended. Here, we introduced a three-dimensional DNA origami as a bioreceptor carrier to functionalize the fiber optic surface plasmon resonance (FO-SPR) sensor with nanoscale precision. Starting from a 24-helix bundle, two distinct DNA origami structures were designed to position thrombin-specific aptamers with different densities and distances (27 and 113 nm) from the FO-SPR surface. The origami-based biosensors not only proved to be capable of reproducible, label-free thrombin detection but revealed also valuable innovative features: (1) a significantly better performance in the absence of backfilling, known as essential in the biosensing field, suggesting improved bioreceptor orientation and accessibility, and (2) a wider linear range compared to previously reported thrombin biosensors. We envisage that our method will be beneficial for both scientists and clinicians looking for new surface (bio)chemistry and improved diagnostics.

Nano-tailored DNA origami designs nanostructure the bioreceptor layer of encoded microparticles in an innovative microfluidic platform, hereby boosting biomolecular interactions.