CREB repressor in mushroom body enhances Drosophila LTM formation

Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, a single training session in an olfactory aversive task is not sufficient to induce protein synthesis-dependent LTM. Instead, multiple spaced training sessions are required. Here, we report that initial learning induces neural activity in the early /{beta} subset of Kenyon cells of the mushroom body (MB), and output from these neurons inhibits LTM formation. Specifically in response to spaced training, Schnurri activates CREBB expression which then appears to suppress the inhibitory output from MB. One training session can enhance LTM formation when this inhibitory effect is relieved. We propose that learning-induced protein synthesis and spaced training-induced CREBB act antagonistically to modulate output from early /{beta} MB neurons during LTM formation.