Ó³»­´«Ã½

Loss-of-function (LoF) mutations of , encoding the GluN2A subunit of N-methyl-D-aspartate receptor (NMDAR), confer a high risk for schizophrenia (SCZ), yet how they affect diverse brain cell types remains poorly understood. Here, we combined subcellular-resolution spatial omics technologies, STARmap and RIBOmap, to jointly resolve single-cell transcriptomes and translatomes for 3,447 genes in the brains of +/- mice and their wild-type littermates across 538,188 cells. Translational dysregulation was markedly more prominent than transcriptional changes in neurons. Across neuronal subtypes, a set of genes including , , , , , and exhibited translational reduction in a gene dose-dependent fashion, suggesting a connection between NMDAR hypofunction and reduced protein synthesis of downstream synaptic plasticity effectors. In interneurons (particularly parvalbumin interneurons), a strong reduction of translation implies loss of inhibitory function in cortical microcircuits, which has long been hypothesized for SCZ pathophysiology. Non-neuronal cell types including astrocytes, oligodendrocytes, and vascular cells also exhibited region-specific translational changes in neurotransmitter transport, lipid synthesis, myelination, and stress response pathways, some of which co-varied with regional neuron state. Together, our study reveals brain-wide translation dysregulation as a critical mechanism underlying SCZ pathophysiology.