1. Repeating or spacing learning sessions are strategies for memory improvement with shared molecular and neuronal components
- Author
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Sergio E. Lew, Alvaro San Martin, Mario Rafael Pagani, Bruce D. Gelb, and Verónica Cattaneo
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Memory, Long-Term ,MAP Kinase Signaling System ,Computer science ,Cognitive Neuroscience ,Experimental and Cognitive Psychology ,Article ,050105 experimental psychology ,purl.org/becyt/ford/1 [https] ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Memory improvement ,Intellectual disability ,medicine ,Animals ,Drosophila Proteins ,Learning ,0501 psychology and cognitive sciences ,MEMORY IMPROVEMENT STRATEGIES ,purl.org/becyt/ford/1.6 [https] ,Mushroom Bodies ,Neurons ,Behavior, Animal ,Repetition (rhetorical device) ,Spacing effect ,05 social sciences ,medicine.disease ,DROSOPHILA ,MEMORY RESCUE ,Mushroom bodies ,RASOPATHIES ,ras Proteins ,Drosophila ,Neuroscience ,030217 neurology & neurosurgery - Abstract
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. Fil: Cattaneo, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina Fil: Gelb, Bruce D.. Mindich Child Health and Development Institute; Estados Unidos Fil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
- Published
- 2020
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