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

## TL;DR

Vitamin D improves smell by controlling how brain cells make and use proteins, linking diet to brain function.

## Contribution

The study reveals a new mechanism where vitamin D regulates synaptic proteins via both transcription and mTOR-dependent translation.

## Key findings

- Vitamin D deficiency impairs odor discrimination, while supplementation enhances olfactory sensitivity.
- Vitamin D signaling in tufted cells of the olfactory bulb involves both transcriptional and translational control of synaptic proteins.
- Rapamycin treatment rescues olfactory deficits in vitamin D-deficient mice by restoring mTOR-mediated translation.

## 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.

Vitamin D (VitD) modulates olfactory function by remodeling dendrodendritic synapses in tufted cells through vitamin D receptor‐dependent transcriptional and translational mechanisms. VitD regulates synaptic protein translation partially via mTOR signaling. Rapamycin rescues VitD deficiency‐induced olfactory deficits by restoring mTOR‐mediated translation, identifying VitD as a diet‐sensitive neuromodulator linking nutrition to synaptic function and sensory processing.