Memory formation is essential for animals to thrive in any environment. I am going to discuss a study from our lab that delineates the effects of different CRH-1 (C. elegans homolog of mammalian CREB1 transcription factor) 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. In order to study the role of CREB1/CRH-1 in C. elegans memory formation, we used CRISPR-Cas9 to make deletions in the different creb1/crh-1 isoforms and saw that of the six CREB1/CRH-1 isoforms found in C. elegans, two of them, CRH-1c and CRH-1e, are primarily responsible for the memory related functions of CREB1/CRH-1 in C. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolished 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 went on to characterize the amino acids K247 and K266 as responsible for the LTM related functions of CREB1/CRH-1. 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.
Using CRISPR-Cas9 to study memory formation in Caenorhabditis elegans
Kavita Babu, Principal Investigator, IISc, Bangalore, India