Notch Intracellular Domain (NICD) Suppresses Long-Term Memory Formation in Adult Drosophila Flies

Notch receptor signaling is evolutionarily conserved and well known for its roles in animal development. Many studies in Drosophila have shown that Notch also performs important functions in memory formation in adult flies. An intriguing observation is that increased expression of the full-length Notch receptor (Nfull) triggers long-term memory (LTM) formation even after very weak training (single training). Canonical Notch signaling is mediated by Notch intracellular domain (NICD), but it is not known whether increased expression of NICD recapitulates the LTM enhancement induced by increased Nfull expression. Here, we report that increased NICD expression either has no impact on LTM formation or suppresses it. Furthermore, it either has no impact or decreases both the levels and activity of cAMP response element binding protein, a key factor supporting LTM. These results indicate that NICD signaling is not sufficient to explain Nfull-induced LTM enhancement. Our findings may also shed light on the molecular mechanisms of memory loss in neurological diseases associated with increased NICD expression and canonical Notch signaling.