Marini Michela, Niu Yabo, Zhao Heng, Mohan Anish, Koorndyk Nathan, Kruyer Anna, Labate Demetrio
Department of Mathematics, University of Houston, Houston, TX, USA.
Division of Pharmaceutical Sciences, University of Cincinnati, Cincinnati, OH, USA.
Sci Adv. 2025 May 2;11(18):eads6841. doi: 10.1126/sciadv.ads6841. Epub 2025 Apr 30.
Astrocytes regulate synaptic activity across large brain territories via their complex, interconnected morphology. Emerging evidence supports the involvement of astrocytes in shaping relapse to opioid use through morphological rearrangements in the nucleus accumbens (NAc). However, a comprehensive assessment of astrocyte structural diversity within and between NAc subdivisions is lacking because of limitations in existing methodologies to quantify meaningful alterations in astrocyte structure. We developed a methodological pipeline that integrates supervised and unsupervised learning techniques to rigorously quantify astrocyte morphological features and spatial organization across the brain, leveraging expression of cytoskeletal markers. Application of this pipeline reveals that morphological characteristics of individual astrocytes predict their location within the NAc. Our analysis also indicates that after heroin use, astrocyte structural plasticity is impaired in portions of the NAc associated with the extinction of conditioned responses and is uniquely engaged in the dorsomedial portion of the NAc shell, an undercharacterized subdivision of the structure.
星形胶质细胞通过其复杂的、相互连接的形态调节大脑大片区域的突触活动。新出现的证据支持星形胶质细胞通过伏隔核（NAc）的形态重排参与阿片类药物使用复发的形成。然而，由于现有方法在量化星形胶质细胞结构中有意义的改变方面存在局限性，缺乏对NAc各亚区内部和之间星形胶质细胞结构多样性的全面评估。我们开发了一种方法流程，该流程整合了监督学习和无监督学习技术，利用细胞骨架标记物的表达，严格量化整个大脑中星形胶质细胞的形态特征和空间组织。应用该流程表明，单个星形胶质细胞的形态特征可预测其在NAc中的位置。我们的分析还表明，使用海洛因后，与条件反应消退相关的NAc部分区域的星形胶质细胞结构可塑性受损，并且在NAc壳的背内侧部分有独特的参与，这是该结构一个特征描述不足的亚区。
