Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
J Comp Neurol. 2022 Sep;530(13):2286-2303. doi: 10.1002/cne.25332. Epub 2022 May 17.
The central nucleus of the amygdala (CeA) network consists of a heterogeneous population of inhibitory GABAergic neurons distributed across distinct subregions. While the specific roles for molecularly defined CeA neurons have been extensively studied, our understanding of functional heterogeneity within classes of molecularly distinct CeA neurons remains incomplete. In addition, manipulation of genetically defined CeA neurons has produced inconsistent behavioral results potentially due to broad targeting across CeA subregions. Therefore, elucidating heterogeneity within molecularly defined neurons in subdivisions of the CeA is pivotal for gaining a complete understanding of how CeA circuits function. Here, we used a multifaceted approach involving transgenic reporter mice, brain slice electrophysiology, and neuronal morphology to dissect the heterogeneity of corticotropin-releasing hormone (CRH) neurons in topographically distinct subregions of the CeA. Our results revealed that intrinsic and morphological properties of CRH-expressing (CRH+) neurons in the lateral (CeL) and medial (CeM) subdivisions of the CeA were significantly different. We found that CeL-CRH+ neurons are relatively homogeneous in morphology and firing profile. Conversely, CeM-CRH+ neurons displayed heterogeneous electrophysiological and morphological phenotypes. Overall, these results show phenotypic differences between CRH+ neurons in CeL and CeM.
杏仁中央核(CeA)网络的核心由分布在不同亚区的异质抑制性 GABA 能神经元组成。虽然已经广泛研究了分子定义的 CeA 神经元的特定作用,但我们对分子上不同的 CeA 神经元的功能异质性的理解仍然不完整。此外,由于 CeA 亚区的广泛靶向,遗传定义的 CeA 神经元的操作产生了不一致的行为结果。因此,阐明 CeA 细分中分子定义神经元内的异质性对于全面了解 CeA 回路的功能至关重要。在这里,我们使用了一种多方面的方法,包括转基因报告小鼠、脑片电生理学和神经元形态学,来剖析 CeA 中拓扑上不同亚区的促肾上腺皮质激素释放激素(CRH)神经元的异质性。我们的结果表明,CeA 中侧部(CeL)和内侧部(CeM)的 CRH 表达(CRH+)神经元的内在和形态特性有显著差异。我们发现 CeL-CRH+神经元在形态和放电模式上相对均匀。相反,CeM-CRH+神经元表现出异质的电生理和形态表型。总的来说,这些结果显示了 CeL 和 CeM 中的 CRH+神经元之间的表型差异。