Open Close
Cattaneo, V., San Martin, A., Lew, S.E., Gelb, B.D., Pagani, M.R. (2020). Repeating or spacing learning sessions are strategies for memory improvement with shared molecular and neuronal components.  Neurobiol. Learn. Mem. 172(): 107233.
FlyBase ID
Publication Type
Research paper

Intellectual disability is a common feature in genetic disorders with enhanced RAS-ERK1/2 signaling, including neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Additional training trials and additional spacing between trials, respectively, restores memory deficits in animal models of NF1 and NS. However, the relationship between the underlying mechanisms in these strategies remain obscure. Here, we developed an approach to examine the effect of adding training trials or spacing to a weak training protocol and used genetic and behavioral manipulations in Drosophila to explore such question. We found that repetition and spacing effects are highly related, being equally effective to improve memory in control flies and sharing mechanistic bases, including the requirement of RAS activity in mushroom body neurons and protein synthesis dependence. After spacing or repeating learning trials, memory improvement depends on the formation of long-term memory (LTM). Moreover, a disease-related gain-of-function RasV152G allele impaired LTM. Using minimal training protocols, we established that both learning strategies were also equally effective for memory rescue in the RasV152G mutant and showed non-additive interaction of the spacing and repetition effects. Memory improvement was never detected after Ras inhibition. We conclude that memory improvement by spacing or repeating training trials are two ways of using the same molecular resources, including RAS-ERK1/2-dependent signaling. This evidence supports the concept that learning problems in RAS-related disorders depend on the impaired ability to exploit the repetition and the spacing effect required for long-term memory induction.

PubMed ID
PubMed Central ID
PMC7451235 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Neurobiol. Learn. Mem.
    Neurobiology of Learning and Memory
    Publication Year
    Data From Reference
    Alleles (6)
    Genes (2)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (1)
    Transgenic Constructs (5)