title: Synaptic evidence for the efficacy of spaced learning.
abstract: The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of F-actin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were "missed" by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA.
authors.forename: Enikö A
authors.initials: EA
authors.lastname: Kramár
authors.forename: Alex H
authors.initials: AH
authors.lastname: Babayan
authors.forename: Cristin F
authors.initials: CF
authors.lastname: Gavin
authors.forename: Conor D
authors.initials: CD
authors.lastname: Cox
authors.forename: Matiar
authors.initials: M
authors.lastname: Jafari
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gall
authors.forename: Gavin
authors.initials: G
authors.lastname: Rumbaugh
authors.forename: Gary
authors.initials: G
authors.lastname: Lynch
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049229:Dendritic Spines / Q000502:physiology; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058105:Polymerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013826:Theta Rhythm / Q000502:physiology; D013997:Time Factors
chemical_list: D000199:Actins