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.
- FGF Homologous Factors
- Learning and Memory