Impaired spatial learning and defective theta burst induced LTP in mice lacking fibroblast growth factor 14.
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.
Wozniak
David F
DF
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Xiao
Maolei
M
Xu
Lin
L
Yamada
Kelvin A
KA
Ornitz
David M
DM
D000161:Acoustic Stimulation; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D004569:Electroencephalography; D004594:Electrophysiology; D005239:Fear / Q000502:physiology / Q000523:psychology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005697:Galactosides; D018737:Hand Strength / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013826:Theta Rhythm
D005697:Galactosides; D007211:Indoles; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside