Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
J Neurosci. 2010 May 19;30(20):6944-53. doi: 10.1523/JNEUROSCI.5772-09.2010.
We have taken a genetic-based fate-mapping approach to determine the specific contributions of telencephalic progenitors to the structures that comprise the amygdalar fear circuit including the central (CA), lateral (LA), and basolateral (BLA) amygdala. Our data indicate that progenitors in the ventral pallium (VP) contribute projection neurons to the LA and BLA but not the CA. Rather, the CA appears to derive, at least in part, from progenitors located in the ventral lateral ganglionic eminence (vLGE). Diverse groups of interneurons populate these amygdalar nuclei, and as predicted our data support the notion that they originate from subpallial progenitors. A rather specific population of amygdalar interneurons, the intercalated cells (ITCs), is known to play a fundamental role in fear-related behaviors. However, no information on their specific origin has, as yet, been provided. Our findings suggest that the ITCs arise from the dorsal lateral ganglionic eminence (dLGE) and migrate in the lateral migratory stream to populate the paracapsular regions as well as the main intercalated mass of the amygdala (IA). Germ-line Gsx2 mutants are known to exhibit an expansion of the VP into the LGE and a concomitant reduction in the dLGE and vLGE. Accordingly, Gsx2 conditional mutants display a significantly enlarged LA and a significant reduction in ITCs both within the paracapsular regions and the IA. Additional support for a dLGE origin of the ITCs was obtained in conditional mutants of the dLGE gene Sp8. Thus, our findings indicate diverse origins for the neuronal components that comprise the amygdalar fear circuit.
我们采用基于遗传的命运映射方法来确定端脑祖细胞对构成杏仁核恐惧回路的结构的具体贡献,包括中央(CA)、外侧(LA)和基底外侧(BLA)杏仁核。我们的数据表明,腹侧苍白球(VP)中的祖细胞向 LA 和 BLA 贡献投射神经元,但不向 CA 贡献。相反,CA 似乎至少部分来源于位于腹外侧神经节隆起(vLGE)的祖细胞。这些杏仁核核团中存在多种中间神经元群体,我们的数据支持它们起源于副皮质祖细胞的观点。已知一种相当特定的杏仁核中间神经元群体,即中间神经元(ITCs),在与恐惧相关的行为中发挥着基本作用。然而,关于它们的具体起源,目前还没有提供任何信息。我们的发现表明,ITCs 起源于背外侧神经节隆起(dLGE),并通过侧迁移流迁移到围绕包膜区域以及杏仁核的主要中间核团(IA)中。已知种系 Gsx2 突变体表现出 VP 扩张进入 LGE,并伴有 dLGE 和 vLGE 的相应减少。因此,Gsx2 条件性突变体显示出 LA 显著增大,以及围绕包膜区域和 IA 中的 ITCs 显著减少。在 dLGE 基因 Sp8 的条件性突变体中获得了 ITCs 的 dLGE 起源的额外支持。因此,我们的研究结果表明,构成杏仁核恐惧回路的神经元成分具有多种起源。