A Polarized Histamine-GABA Core-Rim Architecture within Synaptic Vesicles

Researchers developed a glutaraldehyde-NaBH4 epitope-engineering platform that enables ultrastructural detection of small amines, allowing them to visualize histamine and GABA within individual synaptic vesicles. Quantitative electron microscopy showed histamine condensed into a dense intraluminal core, while GABA immunolabeling was localized predominantly at the vesicle rim. This polarized core-rim organization contrasts with the long-held assumption that clear synaptic vesicles uniformly contain amino acid transmitters, while monoamines reside in dense-core vesicles. The findings may reshape understanding of neurotransmitter packaging, release dynamics, and vesicle recycling, and the new imaging platform could be widely applied to study other small amine transmitters at high resolution.