10 Scopus citations


In contrast to trials of training without intervals (massed training), training trials spaced over time (spaced training) induce a more persistent memory identified as long-term memory (LTM). This phenomenon, known as the spacing effect for memory, is poorly understood.LTMis supported by structural synaptic plasticity; however,howsynapses integrate spaced stimuli remains elusive. Here,we analyzed events of structural synaptic plasticity at the single-synapse level after distinct patterns of stimulation in motoneurons of Drosophila. We found that the spacing effect is a phenomenon detected at synaptic level, which determines the specificity and the precision in structural synaptic plasticity. Whereas a single pulse of stimulation (massed) induced structural synaptic plasticity, the same amount of stimulation divided in three spaced stimuli completely prevented it. This inhibitory effect was determined by the length of the interstimulus intervals. The inhibitory effect of the spacing was lost by suppressing the activity of Ras or mitogen-activated protein kinase, whereas the overexpression of Ras-WT enhanced it. Moreover, dividing the same total time of stimulation into five or more stimuli produced a higher precision in the number of events of plasticity. Ras mutations associated with intellectual disability abolished the spacing effect and led neurons to decode distinct stimulation patterns as massed stimulation. This evidence suggests that the spacing effect for memory may result from the effect of the spacing in synaptic plasticity, which appears to be a property not limited to neurons involved in learning and memory. We propose a model of spacing-dependent structural synaptic plasticity.

Original languageEnglish
Pages (from-to)4992-5007
Number of pages16
JournalJournal of Neuroscience
Issue number19
StatePublished - 10 May 2017


  • Drosophila mononeurons
  • Spaced stimulation
  • Stimulus integration and decoding
  • Structural synaptic plasticity


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