Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Physiol Behav. 2011 Mar 1;102(3-4):323-31. doi: 10.1016/j.physbeh.2010.11.024. Epub 2010 Dec 2.
The Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca(2+)/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.
双皮质素样激酶(DCLK)基因参与发育过程中的神经元迁移。通过选择性剪接,DCLK 基因还产生了一种称为钙调蛋白依赖性蛋白激酶(CaMK)相关肽(CaRP)的转录本,该转录本仅在成年期对神经元活动作出反应时表达。然而,CaRP 的功能仍知之甚少。为了研究 CaRP 的功能,我们生成了在其他脑区(包括海马体)中转录本过表达 CaRP 的转基因小鼠。我们旨在通过使用巴甫洛夫式恐惧条件反射方法来研究这些小鼠可能存在的行为适应。这种类型的恐惧条件反射,其中海马体和杏仁核都至关重要,允许研究与恐惧相关的记忆的形成和消除。我们在此报告两个不同的转基因系的行为适应:一个在海马体和杏仁核中有高水平的 CaRP,而另一个在海马体中有高水平的 CaRP,但在杏仁核中没有。我们通过将它们与野生型同窝仔鼠对照进行比较,分别测试了这两个小鼠系。我们提供的证据表明,两种转基因系的小鼠的上下文恐惧记忆的巩固都得到了加强。