PT - JOURNAL ARTICLE AU - Yogesh Dahiya AU - Saloni Rose AU - Shruti Thapliyal AU - Shivam Bhardwaj AU - Maruthi Prasad AU - Kavita Babu TI - Differential regulation of native and learned behavior by creb1/crh-1 in Caenorhabditis elegans AID - 10.1101/508986 DP - 2019 Jan 01 TA - bioRxiv PG - 508986 4099 - http://biorxiv.org/content/early/2019/01/04/508986.short 4100 - http://biorxiv.org/content/early/2019/01/04/508986.full AB - Memory formation is crucial for the survival of animals. Here, we study the effect of different crh-1 (C. elegans homolog of mammalian CREB1) mutations 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 specific isoforms of CREB1/CRH-1, CRH-1c and CRH-1e, are 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 or AVE neurons is sufficient to rescue long-term memory defects of creb1/crh-1 null mutants. We show that apart from being LTM defective, creb1/crh-1 null mutant animals show defects in native chemotaxis behavior. We go on to characterize the amino acids K247 and K266 as responsible for the LTM related functions of CREB1/CRH-1 while being dispensable for its native chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor and can be further exploited to find CREB1 targets involved in the process of memory formation.