In the mammalian olfactory system, cross-talk between olfactory signals is minimized through physical isolation: individual neurons express one or few olfactory receptors among those encoded in the genome. Physical isolation allows for segregation of stimuli during signal transduction; however, in the nematode worm Caenorhabditis elegans , ∼1,300 olfactory receptors are primarily expressed in only 32 neurons, precluding this strategy. Here, we report genetic and behavioral evidence that β-arrestin–mediated desensitization of olfactory receptors, working downstream of the kinase GRK-1, enables discrimination between intraneuronal olfactory stimuli. Our findings suggest that C. elegans exploits β-arrestin desensitization to maximize responsiveness to novel odors, allowing for behaviorally appropriate responses to olfactory stimuli despite the large number of olfactory receptors signaling in single cells. This represents a fundamentally different solution to the problem of olfactory discrimination than that which evolved in mammals, allowing for economical use of a limited number of sensory neurons.

In the mammalian olfactory system, crosstalk among diverse olfactory signals is minimized through labelled line coding: individual neurons express one or few olfactory receptors among those encoded in the genome. Labelled line coding allows for separation of stimuli during mammalian olfactory signal transduction, however, in the nematode worm Caenorhabditis elegans, 1,300 olfactory receptors are primarily expressed in only 32 neurons, precluding this strategy. Here we report genetic, pharmacological and behavioural evidence that β-arrestin-mediated desensitization of olfactory receptors, working downstream of the kinase GRK-1, enables discrimination between intra-neuronal olfactory stimuli, but that this discrimination relies on quantitative, rather than qualitative differences in signalling. Our findings suggest that C. elegans exploits β-arrestin desensitization to maximize responsiveness to novel odors, allowing for behaviourally appropriate responses to olfactory stimuli despite the large number of olfactory receptors signalling in single cells. This represents a fundamentally different solution to the problem of olfactory discrimination than that which evolved in mammals, allowing for economical use of an extremely limited number of sensory neurons.

Memories are often categorized into types, reflecting their behavioural, anatomical and molecular diversity: these classifications both aid understanding of the differences among varieties of memory and help delineate the unifying cross-species principles underlying them. In the nematode wormCaenorhabditis elegans, we find that an associative memory of the pairing of the normally attractive odorant benzaldehyde and starvation depends on de novo transcription and translation, is independent of CREB, and is produced by massed training: a pattern which does not correspond to any of the well-characterized molecular categories of invertebrate memory. Further, as has been shown for many memories in vertebrates, but not previously in nematodes, we find that formation of this memory continues after removal of the stimuli initially causing it, and that it is labile to disruption through protein synthesis inhibition following training, but that inhibition of proteasomal activity does not extend the duration of the memory. Previous findings have implicated insulin pathway signalling as a key component of this benzaldehyde/starvation memory, however we find that the transcriptional activity required for the memory is likely to be independent of the transcription factors that function at the terminus of this pathway. These findings better characterize this model associative memory in relation to other invertebrate memory types and identify ways in which it both shares their traits and differs from them.