GABAergic inhibitory interneurons of the cerebral cortex expressing vasoactive intestinal peptide (VIP-INs) are rapidly emerging as important regulators of network dynamics and normal circuit development. Several recent studies have also identified VIP-IN dysfunction in models of genetically determined neurodevelopmental disorders (NDDs). In this article, we review the known circuit functions of VIP-INs and how they may relate to accumulating evidence implicating VIP-INs in the mechanisms of prominent NDDs. We highlight recurring VIP-IN-mediated circuit motifs that are shared across cerebral cortical areas and how VIP-IN activity can shape sensory input, development, and behavior. Ultimately, we extract a set of themes that inform our understanding of how VIP-INs influence pathogenesis of NDDs. Using publicly available single-cell RNA sequencing data from the Allen Institute, we also identify several underexplored disease-associated genes that are highly expressed in VIP-INs. We survey these genes and their shared related disease phenotypes that may broadly implicate VIP-INs in autism spectrum disorder and intellectual disability rather than epileptic encephalopathy. Finally, we conclude with a discussion of the relevance of cell type-specific investigations and therapeutics in the age of genomic diagnosis and targeted therapeutics.
Dev Neurosci

中文翻译：

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血管活性肠肽中间神经元在神经发育障碍中的作用

表达血管活性肠肽（VIP-IN）的大脑皮层 GABA 能抑制性中间神经元正在迅速成为网络动态和正常回路发育的重要调节因子。最近的几项研究还发现，遗传决定的神经发育障碍 (NDD) 模型中存在 VIP-IN 功能障碍。在本文中，我们回顾了 VIP-IN 的已知电路功能，以及它们如何与积累的证据相关，这些证据表明 VIP-IN 参与了重要的 NDD 机制。我们重点介绍大脑皮层区域共享的反复出现的 VIP-IN 介导的回路基序，以及 VIP-IN 活动如何塑造感觉输入、发育和行为。最终，我们提取了一组主题，帮助我们理解 VIP-IN 如何影响 NDD 的发病机制。利用艾伦研究所公开的单细胞 RNA 测序数据，我们还鉴定了一些在 VIP-IN 中高表达的尚未充分研究的疾病相关基因。我们调查了这些基因及其共同的相关疾病表型，这些表型可能广泛表明 VIP-IN 与自闭症谱系障碍和智力障碍有关，而不是与癫痫性脑病有关。最后，我们讨论了基因组诊断和靶向治疗时代细胞类型特异性研究和治疗的相关性。
开发神经科学