Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, United States.
Department of Biological Sciences, Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, United States.
Front Neural Circuits. 2024 Jul 17;18:1436915. doi: 10.3389/fncir.2024.1436915. eCollection 2024.
We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so "supertypes," which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions ("t-types" or "clusters"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions.
我们简要（且毫不掩饰地带有偏见）概述了生长抑素中间神经元分类的转录组学前历史，随后按时间顺序总结了过去十年中，美国国立卫生研究院（NIH）支持的大规模研究工作，该工作旨在基于单细胞 RNA 测序生成皮质神经元的综合分类。我们专注于生长抑素中间神经元，展示了实验神经科学家的观点，他们试图将新的分类方案纳入自己的研究中，同时努力跟上不断增加的新提出的细胞类型，这些新提出的细胞类型似乎每两年翻一番。我们认为，对于实验分析，最有用的分类层次是将生长抑素中间神经元细分为十个左右的“超型”，这与它们通过形态学、电生理学和神经化学特征进行的更传统分类密切一致。我们认为，基于基因表达谱的细微差异但缺乏明显表型差异的更精细细分（“t 型”或“簇”）对研究人员的用处较小，实际上可能违背了分类神经元的初衷。最后，我们强调需要生成新的工具（小鼠系、病毒载体）来针对不同的超型进行基因靶向表达，以表达荧光报告基因、钙传感器和兴奋性或抑制性光感受器，使神经科学家能够绘制每个拟议亚型的输入和输出突触连接图，揭示它们在皮质网络中的位置，并在实验中研究它们在感觉运动行为和认知脑功能中的作用。
