Entwined engrams: The evolution of associative and non-associative learning

The nematode Caenorhabditis elegans displays a surprisingly sophisticated behavioral repertoire that includes the utilization of both associative and non-associative forms of learning. Elucidating the molecular basis of learning remains a fundamental, yet daunting, challenge of modern neuroscience. In Pereira and van der Kooy (ref. 2), we described the use of a two input—two output stimuli system to dissociate between associative and non-associative learning and between memory acquisition and retrieval processes. Briefly, one finding indicated that after training with the odorant isoamyl alcohol (IsoA), we could preferentially retrieve either associative or non-associative memory with a choice of either a benzaldehyde (Bnz) or IsoA retrieval stimulus, respectively. Here, we describe how that apparently enigmatic molecular cross wiring of the two forms of memory examined could represent an evolutionary relic of the ancient divergence between non-associative and associative learning. In addition, we extrapolate on the utility and subtleties of using such a system to dissociate and decipher the components of memory in C. elegans.