Asan E, Yilmazer-Hanke D M, Eliava M, Hantsch M, Lesch K-P, Schmitt A
Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
Neuroscience. 2005;131(4):953-67. doi: 10.1016/j.neuroscience.2004.11.040.
Corticotropin-releasing-factor (CRF) containing systems and monoaminergic afferents of the central amygdaloid nucleus (Ce) are crucial players in central nervous stress responses. For functional analyses of specific roles of these systems, numerous mouse models have been generated which lack or overexpress individual signal transduction components. Since data concerning system morphologies in murine brain are rarely available, mouse studies are usually designed and interpreted based on previous findings in rats, although interspecies differences are frequent. In the present study, in situ hybridization for CRF mRNA and correlative immunocytochemistry for CRF and monoaminergic afferents revealed numerous CRF mRNA-reactive neurons in the lateral Ce subnucleus (CeL) codistributed with dense dopaminergic fiber plexus in mice as has been demonstrated in rats. However, while in rats the lateral capsular Ce (CeLc) displays only scarce CRF immunoreactive (CRF-ir) innervation, particularly dense CRF-ir fiber plexus were observed in the CeLc in mice, with differences in labeling densities between different strains. CRF-ir terminal fibers overlap with the moderate serotonergic innervation of this subnucleus in mice. Additionally, CRF mRNA-reactive neurons were found immediately dorsal to the amygdala in the region of the interstitial nucleus of the posterior limb of the anterior commissure/amygdalostriatal transition area in both species. In mice, this region displayed dense CRF-ir fiber plexus, with variations between the strains. The results indicate that in mice and rats dopaminergic afferents represent the primary monoaminergic input to the CRF neurons in the CeL. In mice only, CRF-ir afferents provide dense innervation of CeLc neurons. Since the CeLc lacks dopaminergic input in both species but possesses moderate serotonergic afferents, CRF/serotonin interactions may occur selectively in mouse CeLc. The observed interspecies and interstrain differences in CRF input and CRF/monoaminergic interactions may influence the interpretation of findings concerning Ce functions in stress and fear in mouse models.
促肾上腺皮质激素释放因子（CRF）系统和杏仁中央核（Ce）的单胺能传入神经是中枢神经系统应激反应的关键参与者。为了对这些系统的特定作用进行功能分析，已经构建了许多缺乏或过表达单个信号转导成分的小鼠模型。由于关于小鼠大脑中系统形态的数据很少，尽管种间差异很常见，但小鼠研究通常是基于先前在大鼠中的研究结果进行设计和解释的。在本研究中，CRF mRNA的原位杂交以及CRF和单胺能传入神经的相关免疫细胞化学显示，在小鼠的外侧Ce亚核（CeL）中有大量CRF mRNA反应性神经元，它们与密集的多巴胺能纤维丛共分布，这与在大鼠中所证明的情况相同。然而，虽然在大鼠中，外侧囊状Ce（CeLc）仅显示稀少的CRF免疫反应性（CRF-ir）神经支配，但在小鼠的CeLc中观察到特别密集的CRF-ir纤维丛，不同品系之间的标记密度存在差异。在小鼠中，CRF-ir终末纤维与该亚核的适度5-羟色胺能神经支配重叠。此外，在两个物种的前连合后肢间质核/杏仁核纹状体过渡区的杏仁核背侧立即发现了CRF mRNA反应性神经元。在小鼠中，该区域显示密集的CRF-ir纤维丛，品系之间存在差异。结果表明，在小鼠和大鼠中，多巴胺能传入神经是CeL中CRF神经元的主要单胺能输入。仅在小鼠中，CRF-ir传入神经为CeLc神经元提供密集的神经支配。由于在两个物种中CeLc都缺乏多巴胺能输入，但具有适度的5-羟色胺能传入神经，CRF/5-羟色胺相互作用可能在小鼠CeLc中选择性发生。观察到的CRF输入以及CRF/单胺能相互作用的种间和品系间差异可能会影响对小鼠模型中Ce在应激和恐惧方面功能的研究结果的解释。
