TY - JOUR
T1 - FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons
AU - Shakkottai, Vikram G.
AU - Xiao, Maolei
AU - Xu, Lin
AU - Wong, Michael
AU - Nerbonne, Jeanne M.
AU - Ornitz, David M.
AU - Yamada, Kelvin A.
N1 - Funding Information:
This work was supported by the Hope Center for Neurological Disorders, the National Ataxia Foundation and by an NIH Neuroscience Blueprint Center Core P30 NS057105 grant to Washington University and 1R03NS62431-1. Some of this work was performed in a facility supported by NCRR grant C06 RR015502. The monoclonal antibody FGF14N56/21 was obtained from the UC Davis/NINDS/NIMH NeuroMab Facility, supported by NIH grant U24NS050606 and maintained by the University of California at Davis.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Intracellular fibroblast growth factor 14 (iFGF14)
KW - Nav 1.6
KW - Purkinje neurons
KW - SCA27
KW - Spinocerebellar ataxia
UR - http://www.scopus.com/inward/record.url?scp=57449109506&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2008.09.019
DO - 10.1016/j.nbd.2008.09.019
M3 - Article
C2 - 18930825
AN - SCOPUS:57449109506
SN - 0969-9961
VL - 33
SP - 81
EP - 88
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -