Spaced training rescues memory and ERK1/2 signaling in fragile X syndrome model mice
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Significance: There are no treatments for congenital intellectual disabilities. Here we show that newly discovered timing rules for maximizing hippocampal long-term potentiation predict training regimens that offset defects in synaptic chemistry and memory in the fragile X mental retardation 1 ( Fmr1 ) KO model of fragile X syndrome. Wild-type mice required far less training to form stable memories when given three training trials separated by 1 hour as opposed to one extended session; shorter or longer intervals were ineffective. The same spaced training protocol rescued memory in Fmr1 KO mice and restored activation of synaptic ERK1/2, a kinase critical for both LTP and learning. These results suggest a readily implementable, neurobiologically based therapeutic strategy for a prevalent form of intellectual disability.
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Training with intervals of 60 minutes, but not 20 or 120 minutes, enhanced object recognition learning in wild-type mice and in Fmr1-knockout mice, at least partly by increasing synaptic activation of ERK1 and ERK2.
“Similarly, training with intervals of 60 minutes, but not 20 or 120 minutes, enhanced object recognition learning in wild-type mice and in a mouse model of fragile X syndrome (fragile X mental retardation 1 (Fmr1)-knockout mice), at least partly by increasing synaptic activation of extracellular signal-regulated kinase 1 (ERK1; also known as MAPK3) and ERK2 (also known as MAPK1)67.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [67]
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The right time to learn: Mechanisms and optimization of spaced learning
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- Authors
- Seese, R. R., Wang, K., Yao, Y. Q., Lynch, G., & Gall, C. M.
- Affiliations
- Departments of aAnatomy and Neurobiology,
- University of California, Irvine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-11-10
- Volume
- 111
- Issue
- 47
- Pages
- 16907-16912
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4250145
- OpenAlex
- W1984358896
- Cited by
- 52
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 2 · 2013: 1
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- U.S. Public Health Service (FMH095432A)
- National Institute of Mental Health (R01MH082042, MH082042, F30MH095432)
- National Institute of General Medical Sciences (T32-GM0862)
- National Institute of Neurological Disorders and Stroke (P01NS045260, NS04260)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- spaced training, spaced repetition, fragile X syndrome, Fmr1 knockout mice, object location memory, novel object recognition, recognition memory, long-term potentiation, ERK signaling, dorsal hippocampus, synaptic potentiation, intertrial interval, intellectual disability, learning deficits
- MeSH terms
- Animals, Disease Models, Animal, Fragile X Syndrome, Memory, Signal Transduction, Mice, Knockout, MAP Kinase Signaling System, Mice
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