The Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca2+/calmodulin dependent... Show moreThe Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca2+/calmodulin dependent protein kinase (CaMK)-related peptide (CARP) that is expressed exclusively during adulthood in response to neuronal activity. The function of CARP, however, is poorly understood. To study CARP function, we have generated transgenic mice with over-expression of the CARP transcript in, amongst other brain areas, the hippocampus. We aimed to characterize possible behavioral adaptations of these mice by using a Pavlovian fear conditioning approach. This type of fear conditioning, in which both the hippocampus and amygdala are critically involved, allows studying the formation and extinction of fear related memories. We here report on the behavioral adaptations of two distinct transgenic lines: one with high levels of CARP in the hippocampus and amygdala, whilst the other has high levels of CARP in the hippocampal formation, but not in the amygdala. We tested both mouse lines separately by comparing them to their wild-type littermate controls. We provide evidence suggesting consolidation of contextual fear memories is strengthened in mice of both transgenic lines. (C) 2010 Elsevier Inc. All rights reserved. Show less
Schenk, G.J.; Veldhuisen, B.; Wedemeier, O.; McGown, C.C.; Schouten, T.G.; Oitzl, M.; ... ; Vreugdenhil, E. 2010
Products of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis However the functions of those DCLK gene transcripts that... Show moreProducts of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis However the functions of those DCLK gene transcripts that encode kinases and are expressed during adulthood are Incompletely understood To elucidate potential functions of these DCLK gene splice variants we have generated and analyzed transgenic mice with neuronal over-expression of a truncated constitutively active form of DCLK-short designated delta C-DCLK-short Previously we have performed an extensive molecular characterization of these transgenic delta C-DCLK-short mice and established that a specific subunit of the GABA(A) receptor which is involved in anxiety-related GABAergic neurotransmission is down regulated in the hippocampus Here we show that delta C-DCLK-short mRNA is highly expressed in the hippocampus cortex and amygdala of transgenic mice We provide evidence that the delta C DCLK-short protein is expressed and functional In addition we examined anxiety-related behavior in delta C-DCLK short mice in the elevated plus maze Interestingly delta C-DCLK-short mice spend less time move less in the open arms of the maze and show a reduction in the number of rim dips These behaviors indicate that delta C DCLK-short mice display a more anxious behavioral phenotype (C) 2010 Elsevier Inc All rights reserved Show less
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... 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
