Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14

Maolei Xiao, Lin Xu, Fernanda Laezza, Kelvin Yamada, Sheng Feng, David M. Ornitz

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Humans with an autosomal dominant missense mutation in fibroblast growth factor 14 (FGF14) have impaired cognitive abilities and slowly progressive spinocerebellar ataxia. To explore the mechanisms that may account for this phenotype, we show that synaptic transmission at hippocampal Schaffer collateral-CA1 synapses and short- and long-term potentiation are impaired in Fgf14-/- mice, indicating abnormalities in synaptic plasticity. Examination of CA1 synapses in Fgf14-/- mice show a significant reduction in the number of synaptic vesicles docked at presynaptic active zones and a significant synaptic fatigue/depression during high/low-frequency stimulation. In addition, mEPSC frequency, but not amplitude, is decreased in hippocampal neurons derived from Fgf14-/- mice. Furthermore, expression of selective synaptic proteins in Fgf14-/- mice was decreased. These findings suggest a novel role for FGF14 in regulating synaptic plasticity via presynaptic mechanisms by affecting the mobilization, trafficking, or docking of synaptic vesicles to presynaptic active zones.

Original languageEnglish (US)
Pages (from-to)366-377
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume34
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Neuronal Plasticity
Synaptic Transmission
Synaptic Vesicles
Synapses
Spinocerebellar Ataxias
Long-Term Potentiation
Missense Mutation
Fatigue
Hippocampus
Phenotype
Neurons
fibroblast growth factor 14

Keywords

  • Fibroblast growth factor 14 (FGF14)
  • LTP
  • Synaptic plasticity
  • Synaptic transmission
  • Synaptic vesicles

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14. / Xiao, Maolei; Xu, Lin; Laezza, Fernanda; Yamada, Kelvin; Feng, Sheng; Ornitz, David M.

In: Molecular and Cellular Neuroscience, Vol. 34, No. 3, 03.2007, p. 366-377.

Research output: Contribution to journalArticle

Xiao, Maolei ; Xu, Lin ; Laezza, Fernanda ; Yamada, Kelvin ; Feng, Sheng ; Ornitz, David M. / Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14. In: Molecular and Cellular Neuroscience. 2007 ; Vol. 34, No. 3. pp. 366-377.
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