Differential Regulation of Innate and Learned Behavior by Creb1/Crh-1 in Caenorhabditis elegans

Abstract

Memory formation is crucial for the survival of animals. Here, we study the effect of different crh-1 (C. elegans homolog of mammalian CREB1) isoforms on the ability of C. elegans to form long-term memory (LTM). Null mutants in creb1/crh-1 are defective in LTM formation across phyla. We show that a specific isoform of CREB1/CRH-1, CRH-1e, is primarily responsible for memory related functions of the transcription factor in C. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolishes the long-term memory of the animal. Further, CRH-1e expression in RIM neurons is sufficient to rescue long-term memory defects of creb1/crh-1 null mutants. We go on to show that apart from being LTM defective, creb1/crh-1 null animals show defects in innate chemotaxis behavior. We further characterize the amino acids K247 and K266 as responsible for the LTM related functions of CREB1/CRH-1 while being dispensable for its innate chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor that can be further exploited to find CREB1 targets involved in the process of memory formation.