Abstract:
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.
摘要:
我们提供了促生长素抑制素神经元间分类学的转录前历史的简短(且毫不掩饰地)概述,其次是按时间顺序对大规模的总结,NIH在过去十年中支持的努力,基于单细胞RNA-seq的皮质神经元分类学。专注于生长抑素中间神经元,我们提出了实验神经科学家的观点,试图将新的分类方案纳入他们自己的研究,同时努力跟上不断增加的拟议细胞类型的数量,似乎每两年翻一番.我们建议,为了进行实验分析,最有用的分类学水平是将生长抑素中间神经元细分为十种左右的“超型”,“这与他们更传统的形态学分类非常吻合,电生理和神经化学特征。我们认为更精细的细分(\“t-types\”或\“clusters\”),基于基因表达谱的轻微变化,但缺乏明显的表型差异,对研究人员来说不太有用,实际上可能会破坏对神经元进行分类的目的。最后,我们强调需要生成新的工具(鼠标线,病毒载体)用于遗传靶向不同的超型以表达荧光报道分子,钙传感器和兴奋性或抑制性视蛋白,允许神经科学家绘制每个拟议亚型的输入和输出突触连接图,揭示他们在皮层网络中占据的位置,并通过实验检查他们在感觉运动行为和认知大脑功能中的作用。