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Schenk, G.J.; Werkman, T.; Wadman, W.; Veldhuisen, B.; Dijkmans, T.F.; Blaas, E.; ... ; Vreugdenhil, E. (2010)

Over-expression of the DCLK gene transcript CARP decreases CA3/CA1 network excitability

Article / Letter to editor
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...Show moreProducts 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 hippocam pus. 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. (C) 2010 Elsevier B.V. All rights reserved.Show less
Mouse Field potentials qPCR Calretinin RapGef4 doublecortin-like-kinase acid-lesioned hippocampus mouse dentate gyrus parvalbumin-immunoreactive neurons dependent protein-kinase cell junction formation temporal-lobe epilepsy long-term potentiation ca1 pyramidal neurons kainic acid
All authors
Schenk, G.J.; Werkman, T.; Wadman, W.; Veldhuisen, B.; Dijkmans, T.F.; Blaas, E.; Kegel, L.; Kloet, E.R. de; Vreugdenhil, E.
Date
2010-09-17
Journal
Brain Research
Volume
1352
Pages
21 - 34
DOI
doi:10.1016/j.brainres.2010.07.068