CREB in Mushroom Body Gates Drosophila Long-Term Memory

Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated in 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 learning task is not sufficient to induce protein synthesis-dependent LTM. Instead, multiple spaced training sessions are required. Here, we report the surprising finding that a single training session induces the synthesis of new proteins in early α/β Kenyon cells of the mushroom body (MB), and output from these neurons inhibits LTM formation. CREBB expression, induced by spaced training, then appears to suppress this inhibitory effect. One training session can induce LTM formation when this inhibitory effect is relieved. We propose that learning-induced proteins and spaced training-induced CREBB protein act antagonistically to modulate neuron activity from early α/β MB neurons during LTM formation.