Spaced training rescues memory and ERK1/2 signaling in fragile X syndrome model mice.
Recent studies have shown that short, spaced trains of afferent stimulation produce much greater long-term potentiation (LTP) than that obtained with a single, prolonged stimulation episode. The present studies demonstrate that spaced training regimens, based on these LTP timing rules, facilitate learning in wild-type (WT) mice and can offset learning and synaptic signaling impairments in the fragile X mental retardation 1 (Fmr1) knockout (KO) model of fragile X syndrome. We determined that 5 min of continuous training supports object location memory (OLM) in WT but not Fmr1 KO mice. However, the same amount of training distributed across three short trials, spaced by one hour, produced robust long-term memory in the KOs. At least three training trials were needed to realize the benefit of spacing, and intertrial intervals shorter or longer than 60 min were ineffective. Multiple short training trials also rescued novel object recognition in Fmr1 KOs. The spacing effect was surprisingly potent: just 1 min of OLM training, distributed across three trials, supported robust memory in both genotypes. Spacing also rescued training-induced activation of synaptic ERK1/2 in dorsal hippocampus of Fmr1 KO mice. These results show that a spaced training regimen designed to maximize synaptic potentiation facilitates recognition memory in WT mice and can offset synaptic signaling and memory impairments in a model of congenital intellectual disability.
Departments of Anatomy and Neurobiology.
Ronald R
RR
Seese
Departments of Anatomy and Neurobiology.
Kathleen
K
Wang
Departments of Anatomy and Neurobiology.
Yue Qin
YQ
Yao
Departments of Anatomy and Neurobiology, Psychiatry and Human Behavior, and cmgall@uci.edu glynch@uci.edu.
Gary
G
Lynch
Departments of Anatomy and Neurobiology, Neurobiology and Behavior, University of California, Irvine, CA 92697 cmgall@uci.edu glynch@uci.edu.
Christine M
CM
Gall
D000818:Animals; D004195:Disease Models, Animal; D005600:Fragile X Syndrome / Q000201:enzymology / Q000523:psychology*; D020935:MAP Kinase Signaling System; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction
Fmr1 KO; hippocampus; massed training; novel object recognition; object location memory