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

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.

• Authors: David F Wozniak, Maolei Xiao, Lin Xu, Kelvin A Yamada, David M Ornitz
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 26 Issue 1 Pg. 14-26 (Apr 2007) ISSN: 0969-9961 [Print] United States
• PMID: 17236779 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Galactosides
• Indoles
• fibroblast growth factor 14
• Fibroblast Growth Factors
• 5-bromo-4-chloro-3-indolyl beta-galactoside

Topics

• Acoustic Stimulation
• Animals
• Avoidance Learning (physiology)
• Conditioning, Psychological (physiology)
• Cues
• Electroencephalography
• Electrophysiology
• Fear (physiology, psychology)
• Fibroblast Growth Factors (genetics, physiology)
• Galactosides
• Hand Strength (physiology)
• Hippocampus (metabolism, physiology)
• Immunohistochemistry
• In Situ Hybridization
• Indoles
• Long-Term Potentiation (physiology)
• Male
• Maze Learning (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity (physiology)
• Postural Balance (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Theta Rhythm