NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain

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