Learning capacity is known to decline with age, and similar effects are also associated with several neurodegenerative diseases. Regulation of insulin signaling by dietary restriction modulates lifespan in many organisms, and it has been also shown to enhance learning and memory. However, the underlying mechanisms of these processes are largely unknown due to the difficulty in disentangling the systemic effects of dietary restriction from any potentially brain-specific effects. This study by Vohra et al. analyzes the molecular effects of dietary restriction in the nematode Caenorhabditis elegans and shows that associative learning is enhanced by reducing production of the tryptophan metabolite kynurenic acid. Kynurenic acid is an antagonist of glutamatergic signaling in neurons, and the authors find that its depletion in the nervous system by dietary restriction allows for increased activation of an interneuron that helps mediate learning. Kynurenic acid levels seem to have no effect on organismal lifespan, indicating that the effects of this response to dietary restriction are specific to brain function. This image shows the body of a nematode with its entire nervous system visualized using green fluorescent protein.

Image Credit: Hang Ung