Fig. 6.

Proposed model of synaptic changes with VitD3. Optimal levels of VitD3 stabilize myelin structure and enhance synaptic vesicle recycling and transcription factors facilitating cognitive processes. Together, these changes preserve memory in aging. (Inset) Anchoring of the myelin to the axon facilitated by contactin. (Presynaptic targets) Empty clathrin-coated vesicles undergo endocytosis or recycling driven, in part, by the phosphatase synaptojanin 1. Vesicle refilling of glutamate (red molecules) occurs via vesicular glutamate transporter 2 (VGLUT2). Ca²⁺ enters the synapse via kainate receptor 3 (Grik3), and docking of the filled vesicle is facilitated by Ca²⁺ binding to synaptotagmin 2. The synapse also contains a dopamine-filled synaptic vesicle (purple molecules), which can colocalize with kainate receptor 3 terminals. (Postsynaptic targets) Stimulation of glutamate (or dopamine 5) receptors initiates a CaMKIIδ signaling cascade resulting in activation of transcription factors (CREB3 and NR4A2) and subsequent expression of genes promoting memory-related processes. (Illustration by Tom Dolan, University of Kentucky.)