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

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.