Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical, and physiological properties. However, the molecular mechanisms regulating their maturation remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates transcriptional regulation of gene expression in specific subtypes of MGE-derived interneurons, leading to altered subtype abundances. Notably, MGE-specific early developmental Grin1 loss results in a broad downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs in the juvenile brain. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.

内侧神经节隆起 (MGE) 衍生的小清蛋白 (PV)+、生长抑素 (SST)+ 和神经胶质细胞 (NGFC) 型皮质和海马中间神经元具有独特的分子、解剖和生理特性。然而，调控其成熟的分子机制仍然知之甚少。在这里，通过单细胞转录组学，我们显示专性 NMDA 型谷氨酸受体 (NMDAR) 亚基基因咧嘴一笑在 MGE 衍生的中间神经元的特定亚型中介导基因表达的转录调控，导致亚型丰度的改变。值得注意的是，MGE 特异性早期发育 Grin1 丢失导致幼年大脑中各种转录、突触和膜兴奋性调节程序的广泛下调。这些广泛的基因表达异常反映了通常与神经发育障碍相关的畸变。因此，我们的研究为系统检查中间神经元亚型中的 NMDAR 信号提供了路线图，揭示了潜在的 MGE 特异性遗传目标，可以指导未来的精神疾病治疗。