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PMID: 18930825 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons.

Neurobiology of disease ·Vol. 33 ·No. 1 ·2009-01-00 ·Pages 81-8

Shakkottai VG, Xiao M, Xu L, Wong M, Nerbonne JM, Ornitz DM, Yamada KA

Abstract

A missense mutation in the fibroblast growth factor 14 (FGF14) gene underlies SCA27, an autosomal dominant spinocerebellar ataxia in humans. Mice with a targeted disruption of the Fgf14 locus (Fgf14(-/-)) develop ataxia resembling human SCA27. We tested the hypothesis that loss of FGF14 affects the firing properties of Purkinje neurons, which play an important role in motor control and coordination. Current clamp recordings from Purkinje neurons in cerebellar slices revealed attenuated spontaneous firing in Fgf14(-/-) neurons. Unlike in the wild type animals, more than 80% of Fgf14(-/-) Purkinje neurons were quiescent and failed to fire repetitively in response to depolarizing current injections. Immunohistochemical examination revealed reduced expression of Nav1.6 protein in Fgf14(-/-) Purkinje neurons. Together, these observations suggest that FGF14 is required for normal Nav1.6 expression in Purkinje neurons, and that the loss of FGF14 impairs spontaneous and repetitive firing in Purkinje neurons by altering the expression of Nav1.6 channels.

MeSH Terms
Action Potentials Animals Cerebellum/physiology Excitatory Postsynaptic Potentials Fibroblast Growth Factors/genetics,metabolism Immunohistochemistry In Situ Hybridization In Vitro Techniques Mice Mice, Inbred C57BL Mice, Knockout NAV1.6 Voltage-Gated Sodium Channel Nerve Tissue Proteins/metabolism Patch-Clamp Techniques Purkinje Cells/physiology Sodium Channels/metabolism
Chemicals
NAV1.6 Voltage-Gated Sodium Channel Nerve Tissue Proteins Scn8a protein, mouse Sodium Channels fibroblast growth factor 14 Fibroblast Growth Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shakkottai Vikram G
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Xiao Maolei
Xu Lin
Wong Michael
Nerbonne Jeanne M
Ornitz David M
Yamada Kelvin A
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Article Info
Journal
Neurobiology of disease
Abbr.
Neurobiol Dis
ISSN
1095-953X
DOI
10.1016/j.nbd.2008.09.019
Published
2009-01-00
Epub
2008-00-01
Pages
81-8
Language
English
Region
United States
NLM ID
9500169
PMCID
PMC2652849
Subset
IM
Grants
NINDS NIH HHS · P30 NS057105 · United States
NINDS NIH HHS · U24 NS050606 · United States
NINDS NIH HHS · P30 NS057105-01 · United States
NINDS NIH HHS · U24NS050606 · United States
NINDS NIH HHS · R03 NS062431 · United States
NCRR NIH HHS · C06 RR015502 · United States
NINDS NIH HHS · R03 NS062431-01 · United States
External Links
PubMed source DOI: 10.1016/j.nbd.2008.09.019 PMC Full Text View journal details
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