Vagal afferent neurons projecting to the stomach and small intestine exhibit multiple N-methyl-D-aspartate receptor...

Previous reports suggest that NMDA receptors participate in control of food intake via vagal afferent neurons that innervate the upper gastrointestinal (GI) tract. While messenger RNA coding for the NR1 NMDA receptor subunit is present in a majority of vagal afferent neurons of nodose ganglia (NG), immunoreactivity for other NMDA receptor subunits (NR2B, NR2C and NR2D) are expressed in more limited subpopulations of vagal afferents. To determine whether vagal afferent neurons that project to the stomach or duodenum exhibit distinct NMDA receptor subunit phenotypes, we examined immunoreactivity (IR) for NMDA receptor NR1, NR2B, NR2C and NR2D subunits in NG neurons that were labeled by injections of the retrograde tracer Fast Blue (FB) into the wall of the stomach or duodenum. FB injections into the fundus or corpus of the stomach labeled comparable numbers of neurons in both the left and right NG, while proximal duodenal injections labeled only neurons of left NG. NR1-IR expression was observed in most neurons innervating the upper GI tract (fundus, 97%; corpus, 95%; duodenum, 98%). Likewise, most neurons that innervated the upper GI tract expressed NR2B-IR (fundus, 98%; corpus, 85%; duodenum, 81%). NR2C-IR was observed in only 52%, 46% and 32% of FB-positive neurons projecting to the fundus, corpus or duodenum respectively, while NR2D-IR occurred in an even more restricted FB-labeled subpopulation (fundus, 13%; corpus, 26%; and duodenum, 18%). Our observations indicate that different subpopulations of vagal afferents express distinct NMDA receptor subunit phenotypes. However, the neuronal distribution of NMDA receptor subunits is not correlated with innervation of either the stomach or duodenum.