Cortical neuronal networks control cognitive output, but their composition and modulation remain elusive. Here, we studied the morphological and transcriptional diversity of cortical cholinergic VIP/ChAT interneurons (VChIs), a sparse population with a largely unknown function. We focused on VChIs from the whole barrel cortex and developed a high-throughput automated reconstruction framework, termed PopRec, to characterize hundreds of VChIs from each mouse in an unbiased manner, while preserving 3D cortical coordinates in multiple cleared mouse brains, accumulating thousands of cells. We identified two fundamentally distinct morphological types of VChIs, bipolar and multipolar that differ in their cortical distribution and general morphological features. Following mild unilateral whisker deprivation on postnatal day seven, we found after three weeks both ipsi- and contralateral dendritic arborization differences and modified cortical depth and distribution patterns in the barrel fields alone. To seek the transcriptomic drivers, we developed NuNeX, a method for isolating nuclei from fixed tissues, to explore sorted VChIs. This highlighted differentially expressed neuronal structural transcripts, altered exitatory innervation pathways and established Elmo1 as a key regulator of morphology following deprivation.

中文翻译：

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高通量形态学和转录组学分析揭示了幼稚和感觉剥夺的皮质胆碱能 VIP/CHAT 神经元的组成

皮层神经元网络控制认知输出，但它们的组成和调节仍然难以捉摸。在这里，我们研究了皮质胆碱能 VIP/ChAT 中间神经元 (VChIs) 的形态和转录多样性，这是一个功能未知的稀疏种群。我们专注于来自整个桶状皮质的 VChI，并开发了一个高通量自动重建框架，称为 PopRec，以无偏见的方式表征每只小鼠的数百个 VChI，同时在多个清除的小鼠大脑中保留 3D 皮质坐标，积累数千个细胞. 我们确定了两种根本不同的 VChI 形态类型，双极和多极，它们的皮质分布和一般形态特征不同。在产后第七天轻度单侧胡须剥夺后，三周后，我们发现同侧和对侧树突状树枝化差异以及单独在桶状区域中的皮质深度和分布模式发生了变化。为了寻找转录组驱动因素，我们开发了 NuNeX，这是一种从固定组织中分离细胞核的方法，用于探索分类的 VChI。这突出了差异表达的神经元结构转录物，改变了兴奋性神经支配途径，并将 Elmo1 确立为剥夺后形态学的关键调节因子。