Vesicular glutamate transporter 2 in the brain–gut axis

Previous reports have indicated that vesicular glutamate transporters (VGLUTs) are found only in central neurons. We show that neurons in the gut, which also contain glutamate and markers of intrinsic primary afferent neurons, display VGLUT2 immunoreactivity in several species, including humans. Glutamatergic (VGLUT2-immunoreactive) varicosities, which often co-stored choline acetyltransferase and the vesicular acetylcholine transporter, were apposed to a subset of nerve cell bodies in the submucosal and myenteric plexus. Retrograde tracing with FluoroGold demonstrated that VGLUT2 is found in nodose and dorsal root ganglia neurons innervating the stomach. Thus, VGLUT2 is found in intrinsic and extrinsic primary afferent neurons, which suggests that glutamate is as primary afferent neurotransmitter that transfers information from the mucosa to the enteric plexuses and brain.