Coyner Jennifer, McGuire Jennifer L, Parker Clarissa C, Ursano Robert J, Palmer Abraham A, Johnson Luke R
Program in Neuroscience and Department of Psychiatry, Uniformed Services University (USU), School of Medicine, Bethesda, MD 20814, USA.
Department of Human Genetics, University of Chicago, IL, USA.
Neurobiol Learn Mem. 2014 Jul;112:195-203. doi: 10.1016/j.nlm.2013.06.010. Epub 2013 Jun 28.
Individual variability in the acquisition, consolidation and extinction of conditioned fear potentially contributes to the development of fear pathology including posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a key tool for the study of fundamental aspects of fear learning. Here, we used a selected mouse line of High and Low Pavlovian conditioned fear created from an advanced intercrossed line (AIL) in order to begin to identify the cellular basis of phenotypic divergence in Pavlovian fear conditioning. We investigated whether phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for the acquisition and consolidation of Pavlovian fear memory, is differentially expressed following Pavlovian fear learning in the High and Low fear lines. We found that following Pavlovian auditory fear conditioning, High and Low line mice differ in the number of pMAPK-expressing neurons in the dorsal sub nucleus of the lateral amygdala (LAd). In contrast, this difference was not detected in the ventral medial (LAvm) or ventral lateral (LAvl) amygdala sub nuclei or in control animals. We propose that this apparent increase in plasticity at a known locus of fear memory acquisition and consolidation relates to intrinsic differences between the two fear phenotypes. These data provide important insights into the micronetwork mechanisms encoding phenotypic differences in fear. Understanding the circuit level cellular and molecular mechanisms that underlie individual variability in fear learning is critical for the development of effective treatment of fear-related illnesses such as PTSD.
条件性恐惧的获得、巩固和消退过程中的个体差异可能会导致包括创伤后应激障碍(PTSD)在内的恐惧病理学的发展。巴甫洛夫式恐惧条件反射是研究恐惧学习基本方面的关键工具。在此,我们使用了从高级杂交系(AIL)培育出的高、低巴甫洛夫式条件性恐惧的特定小鼠品系,以便开始确定巴甫洛夫式恐惧条件反射中表型差异的细胞基础。我们研究了磷酸化丝裂原活化蛋白激酶(p44/42 ERK/MAPK),一种杏仁核中获得和巩固巴甫洛夫式恐惧记忆所需的蛋白激酶,在高恐惧和低恐惧品系的巴甫洛夫式恐惧学习后是否有差异表达。我们发现,在巴甫洛夫式听觉恐惧条件反射后,高恐惧和低恐惧品系小鼠在外侧杏仁核背侧亚核(LAd)中表达pMAPK的神经元数量上存在差异。相比之下,在杏仁核腹内侧(LAvm)或腹外侧(LAvl)亚核或对照动物中未检测到这种差异。我们认为,在已知的恐惧记忆获得和巩固位点上这种明显的可塑性增加与两种恐惧表型之间的内在差异有关。这些数据为编码恐惧表型差异的微网络机制提供了重要见解。了解恐惧学习中个体差异背后的回路水平细胞和分子机制对于开发有效治疗PTSD等恐惧相关疾病至关重要。