Impaired spatial learning and defective theta burst induced LTP in mice lacking fibroblast growth factor 14

David F. Wozniak, Maolei Xiao, Lin Xu, Kelvin A. Yamada, David M. Ornitz

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Spinocerebellar ataxia 27 (SCA27) is a recently described syndrome characterized by impaired cognitive abilities and a slowly progressive ataxia. SCA27 is caused by an autosomal dominant missense mutation in Fibroblast Growth Factor 14 (FGF14). Mice lacking FGF14 (Fgf14-/- mice) have impaired sensorimotor functions, ataxia and paroxysmal dyskinesia, a phenotype that led to the discovery of the human mutation. Here we extend the similarities between Fgf14-/- mice and FGF14(F145S) humans by showing that Fgf14-/- mice exhibit reliable acquisition (place learning) deficits in the Morris water maze. This cognitive deficit appears to be independent of sensorimotor disturbances and relatively selective since Fgf14-/- mice performed similarly to wild type littermates during cued water maze trials and on conditioned fear and passive avoidance tests. Impaired theta burst initiated long-term synaptic potentiation was also found in hippocampal slices from Fgf14-/- mice. These results suggest a role for FGF14 in certain spatial learning functions and synaptic plasticity.

Original languageEnglish
Pages (from-to)14-26
Number of pages13
JournalNeurobiology of Disease
Volume26
Issue number1
DOIs
StatePublished - Apr 2007

Keywords

  • Behavior
  • Cognition
  • FGF Homologous Factors
  • FGF14
  • Hippocampus
  • LTP
  • Learning and Memory

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