TY - JOUR
T1 - Over-expression of the DCLK gene transcript CARP decreases CA3/CA1 network excitability
AU - Schenk, Geert J.
AU - Werkman, Taco
AU - Wadman, Wytse
AU - Veldhuisen, Barbera
AU - Dijkmans, Thomas F.
AU - Blaas, Eva
AU - Kegel, Linde
AU - de Kloet, E. Ron
AU - Vreugdenhil, Erno
PY - 2010/9/17
Y1 - 2010/9/17
N2 - Products of the Doublecortin Like Kinase (DCLK) gene are implicated in cortical migration and hippocampal maturation during embryogenesis. However, one of its splice variants, called CaMK Related Peptide (CARP), is expressed during adulthood in response to neurological stimuli, such as kainic acid-induced seizures and BDNF-LTP. The function of this transcript of the DCLK gene is poorly understood. To elucidate its function during adulthood we have created transgenic mice with over-expression of CARP in the brain. To study potential functions of CARP in the hippocampus we performed an electrophysiological characterization of the CA3/CA1 network of transgenic and wild-type mice and showed that field excitatory post synaptic potentials (fEPSPs) are highly increased in transgenic mice, while population spike amplitudes (PSAs) remained equal between genotypes. Consequently, hippocampal CA3/CA1 network excitability was decreased in transgenic mice. In addition we show a 2-fold up-regulation of the Ca2+-binding protein calretinin and a down-regulation of Rapgef4, a guanine exchange factor for Rap1, in the hippocampus. Given previously established conditions during which CARP is induced and our current data, we propose that this DCLK gene product affects glutamatergic neuronal transmission in response to neurological stimuli. © 2010 Elsevier B.V. All rights reserved.
AB - Products of the Doublecortin Like Kinase (DCLK) gene are implicated in cortical migration and hippocampal maturation during embryogenesis. However, one of its splice variants, called CaMK Related Peptide (CARP), is expressed during adulthood in response to neurological stimuli, such as kainic acid-induced seizures and BDNF-LTP. The function of this transcript of the DCLK gene is poorly understood. To elucidate its function during adulthood we have created transgenic mice with over-expression of CARP in the brain. To study potential functions of CARP in the hippocampus we performed an electrophysiological characterization of the CA3/CA1 network of transgenic and wild-type mice and showed that field excitatory post synaptic potentials (fEPSPs) are highly increased in transgenic mice, while population spike amplitudes (PSAs) remained equal between genotypes. Consequently, hippocampal CA3/CA1 network excitability was decreased in transgenic mice. In addition we show a 2-fold up-regulation of the Ca2+-binding protein calretinin and a down-regulation of Rapgef4, a guanine exchange factor for Rap1, in the hippocampus. Given previously established conditions during which CARP is induced and our current data, we propose that this DCLK gene product affects glutamatergic neuronal transmission in response to neurological stimuli. © 2010 Elsevier B.V. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77956173645&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/20659433
U2 - https://doi.org/10.1016/j.brainres.2010.07.068
DO - https://doi.org/10.1016/j.brainres.2010.07.068
M3 - Article
C2 - 20659433
SN - 0006-8993
VL - 1352
SP - 21
EP - 34
JO - Brain Research
JF - Brain Research
ER -