New York University Neuroscience Institute, New York University Grossman School of Medicine, New York University, New York, NY 10016.
Department of Neuroscience and Physiology, New York University, New York, NY 10016.
Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2306382121. doi: 10.1073/pnas.2306382121. Epub 2024 Apr 19.
Hippocampal somatostatin-expressing () GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive -IN subpopulations census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of -INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal INs that largely tiled the morpho-functional parameter space of the -INs superfamily. Notably, the intersection revealed a population of bistratified INs that preferentially synapsed onto fast-spiking interneurons (FS-INs) and were sufficient to interrupt their firing. In contrast, the intersection identified a population of oriens lacunosum-moleculare INs that predominantly targeted CA1 pyramidal neurons, avoiding FS-INs. Overall, our results provide a framework to translate neuronal transcriptomic identity into discrete functional subtypes that capture the diverse specializations of hippocampal -INs.
海马体中表达生长抑素的（）GABA 能中间神经元（INs）表现出相当大的解剖和功能异质性。最近的单细胞转录组分析提供了一个全面的-IN 亚群普查，这是神经元身份的合理分子基础，但与特定功能的联系仍不完整。在这里，我们设计了一种基于转录组特征来识别和访问-IN 亚群的方法。基于单个或组合 Cre 和 Flp 表达的四种小鼠模型区分了 CA1 海马 INs 的功能不同的亚群，这些亚群在很大程度上覆盖了-INs 超家族的形态-功能参数空间。值得注意的是，交集揭示了一个双分层 INs 群体，它们优先与快速放电中间神经元（FS-INs）形成突触，并足以中断其放电。相比之下，交集确定了一个或iens lacunosum-moleculare INs 群体，它们主要靶向 CA1 锥体神经元，避免与 FS-INs 形成突触。总的来说，我们的结果提供了一个将神经元转录组身份转化为离散功能亚型的框架，这些亚型可以捕捉到海马体-INs 的多样化特化。
