OBJECTIVE Theories of amygdala function are central to our understanding of psychiatric and neurodevelopmental disorders. However, limited knowledge of the molecular and cellular composition of the amygdala impedes translational research aimed at developing new treatments and interventions. The aim of this study was to characterize and compare the composition of amygdala cells to help bridge the gap between preclinical models and human psychiatric and neurodevelopmental disorders. METHODS Tissue was dissected from multiple amygdala subnuclei in both humans (N=3, male) and rhesus macaques (N=3, male). Single-nucleus RNA sequencing was performed to characterize the transcriptomes of individual nuclei. RESULTS The results reveal substantial heterogeneity between regions, even when restricted to inhibitory or excitatory neurons. Consistent with previous work, the data highlight the complexities of individual marker genes for uniquely targeting specific cell types. Cross-species analyses suggest that the rhesus monkey model is well-suited to understanding the human amygdala, but also identify limitations. For example, a cell cluster in the ventral lateral nucleus of the amygdala (vLa) is enriched in humans relative to rhesus macaques. Additionally, the data describe specific cell clusters with relative enrichment of disorder-related genes. These analyses point to the human-enriched vLa cell cluster as relevant to autism spectrum disorder, potentially highlighting a vulnerability to neurodevelopmental disorders that has emerged in recent primate evolution. Further, a cluster of cells expressing markers for intercalated cells is enriched for genes reported in human genome-wide association studies of neuroticism, anxiety disorders, and depressive disorders. CONCLUSIONS Together, these findings shed light on the composition of the amygdala and identify specific cell types that can be prioritized in basic science research to better understand human psychopathology and guide the development of potential treatments.

中文翻译：

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恒河猴和人类杏仁核亚核细胞类型变异的转化见解。


目的 杏仁核功能理论是我们理解精神和神经发育障碍的核心。然而，对杏仁核分子和细胞组成的了解有限，阻碍了旨在开发新疗法和干预措施的转化研究。本研究的目的是表征和比较杏仁核细胞的组成，以帮助弥合临床前模型与人类精神和神经发育障碍之间的差距。方法 从人类 （N=3，雄性） 和恒河猴 （N=3，雄性） 的多个杏仁核亚核中解剖组织。进行单核 RNA 测序以表征单个细胞核的转录组。结果结果显示区域之间存在很大的异质性，即使仅限于抑制性或兴奋性神经元也是如此。与以前的工作一致，这些数据突出了独特靶向特定细胞类型的单个标记基因的复杂性。跨物种分析表明，恒河猴模型非常适合理解人类杏仁核，但也发现了局限性。例如，相对于恒河猴，杏仁核 （vLa） 腹侧核 （vLa） 中的细胞簇在人类中富集。此外，这些数据描述了具有疾病相关基因相对富集的特定细胞簇。这些分析指出，人类富集的 vLa 细胞簇与自闭症谱系障碍相关，可能突出了最近灵长类动物进化中出现的神经发育障碍的脆弱性。此外，表达嵌入细胞标志物的细胞簇富集了神经质、焦虑症和抑郁症的人类全基因组关联研究中报道的基因。 结论总之，这些发现阐明了杏仁核的组成，并确定了可以在基础科学研究中优先考虑的特定细胞类型，以更好地了解人类精神病理学并指导潜在治疗方法的开发。