CGG trinucleotide repeat length modulates neural plasticity and spatiotemporal processing in a mouse model of the fragile X premutation

Michael R. Hunsaker, Kyoungmi Kim, Rob Willemsen, Robert F Berman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 70-198 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.

Original languageEnglish (US)
Pages (from-to)2260-2275
Number of pages16
JournalHippocampus
Volume22
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Trinucleotide Repeats
Neuronal Plasticity
Cognition
Endophenotypes
Inborn Genetic Diseases
Genes
metabotropic glutamate receptor type 1

Keywords

  • CGG KI mouse
  • Endophenotype
  • Fragile X permutation
  • Long-term depression
  • Long-term potentiation
  • Pattern separation
  • Spatial processing
  • Spatiotemporal hypergranularity
  • Temporal order

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

CGG trinucleotide repeat length modulates neural plasticity and spatiotemporal processing in a mouse model of the fragile X premutation. / Hunsaker, Michael R.; Kim, Kyoungmi; Willemsen, Rob; Berman, Robert F.

In: Hippocampus, Vol. 22, No. 12, 12.2012, p. 2260-2275.

Research output: Contribution to journalArticle

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