Journal
HIPPOCAMPUS
Volume 22, Issue 12, Pages 2260-2275Publisher
WILEY
DOI: 10.1002/hipo.22043
Keywords
fragile X permutation; CGG KI mouse; long-term potentiation; long-term depression; pattern separation; temporal order; spatial processing; spatiotemporal hypergranularity; pattern separation; endophenotype
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Funding
- National Institute of Health (NIH) [NINDS RL1 NS062411]
- Roadmap Initiative grant, NIDCR [UL1 DE019583]
- NeuroTherapeutics Research Institute (NTRI), NCRR [UL1 RR024146]
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The fragile X premutation is a CGG repeat expansion on the FMR1 gene between 55 and 200 repeats in length. It has been proposed that impaired spatiotemporal function underlies cognitive deficits in genetic disorders, including the fragile X premutation. This study characterized the role of the premutation for cognitive function by demonstrating CGG KI mice with 70198 CGG repeats show deficits across tasks requiring spatial and temporal pattern separation. To elucidate mechanisms whereby CGG repeats affect spatiotemporal processing, hippocampal slices were evaluated for LTP, LTD, and mGluR1/5 LTD. Increasing CGG repeat length modulated the induction of LTP, LTD, and mGluR1/5 LTD, as well as behavioral tasks emphasizing spatiotemporal processing. Despite the deficits in the induction of all forms of plasticity, there were no differences in expression of plasticity once evoked. These data provide evidence for a neurocognitive endophenotype in the CGG KI mouse model of the premutation in which CGG repeat length negatively modulates plasticity and spatiotemporal attention. (c) 2012 Wiley Periodicals, Inc.
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