Two forms of learning following training to a single odorant in Caenorhabditis elegans AWC neurons

The nematode Caenorhabditis elegans can adapt to both the AWC-sensed odorants benzaldehyde (Bnz) and isoamyl alcohol (IsoA) and can reciprocally cross-adapt. Yet we reveal that these four adaptation scenarios actually represent two distinct forms of learning: nonassociative habituation and associative learning by pairing with a starvation unconditioned stimulus. Training to the single odorant IsoA leads to both associative and nonassociative memory traces, which can be preferentially accessed by either a Bnz or IsoA retrieval stimulus, respectively. This represents the first demonstration in which the form of learning displayed after training to a single stimulus is a function of the retrieval stimulus used. Furthermore, these two forms of learning can be genetically double dissociated despite both forms occurring within the AWC primary sensory neuron. We find that associative learning requires the cGMP-dependent kinase egl-4 and insulin signaling, which acts downstream of egl-4. In contrast, nonassociative learning requires neither of these genes, but does require the TRPV channel osm-9, which is dispensable for associative learning. In addition, we find that the arrestin arr-1 is promiscuous between associative and nonassociative learning in mediating the adaptive response to the IsoA retrieval stimulus, suggesting that distinct forms of memory may nonetheless use common downstream effectors.