CREBA and CREBB in two identified neurons gate long-term memory formation in <i>Drosophila</i>

Abstract

Episodic events are frequently consolidated into labile memory but are not necessarily transferred to persistent long-term memory (LTM). Regulatory mechanisms leading to LTM formation are poorly understood, however, especially at the resolution of identified neurons. Here, we demonstrate enhanced LTM following aversive olfactory conditioning in <i>Drosophila</i> when the transcription factor cyclic AMP response element binding protein A (CREBA) is induced in just two dorsal-anterior-lateral (DAL) neurons. Our experiments show that this process is regulated by protein-gene interactions in DAL neurons: (1) <i>crebA</i> transcription is induced by training and repressed by <i>crebB</i> overexpression, (2) CREBA bidirectionally modulates LTM formation, (3) <i>crebA</i> overexpression enhances training-induced gene transcription, and (4) increasing membrane excitability enhances LTM formation and gene expression. These findings suggest that activity-dependent gene expression in DAL neurons during LTM formation is regulated by CREB proteins.