Vitamin D Regulates Olfactory Function via Dual Transcriptional and mTOR‐Dependent Translational Control of Synaptic Proteins

Abstract Vitamin D (VitD) deficiency is associated with neurological dysfunction, but its cell‐type‐specific mechanisms remain poorly understood. Using mice with controlled VitD levels from weaning through adulthood, it is demonstrated that VitD regulates olfactory function through vitamin D receptors (VDR). Deficiency impairs odor discrimination, whereas supplementation enhances sensitivity—phenotypes recapitulated by olfactory‐specific VDR knockdown. Single‐nucleus RNA sequencing (snRNA‐seq) and spatial transcriptomics reveal enriched VDR expression selectively in olfactory bulb tufted cells, where VitD signaling mediates dendrodendritic synaptic remodeling via both transcriptional and translational mechanisms in a VDR‐dependent manner. Notably, VitD modulates synaptic protein expression partly through mechanistic target of rapamycin (mTOR) signaling, and rapamycin treatment restores translational homeostasis and olfactory function in VitD‐deficient mice. Chromatin immunoprecipitation sequencing (ChIP‐seq) confirms direct VDR binding to genes encoding synaptic proteins and translational machinery components, including mTOR pathway effectors. Together, these results identify a novel VDR‐mTOR‐translational regulatory axis that operates alongside classical transcriptional regulation, establishing VitD as a diet‐sensitive neuromodulator that links nutritional status to synaptic function and sensory processing.