Food-related gastrointestinal signals activate caudal brainstem neurons expressing both NMDA and AMPA receptors

Vagal mechano- and chemosensors in the gastrointestinal tract and the portal-hepatic axis signaling the arrival of nutrients are major determinants of the satiation process. Although glutamate and its various receptor subtypes have been shown to transmit gustatory and cardiovascular sensory information at the level of the solitary nucleus (nucleus tractus solitarius; NTS), their involvement in the transmission of gastrointestinal satiety signals is not clear. Gastrointestinal sensors were stimulated by gastric balloon distension or by intraduodenal infusion of either linoleic acid or glucose in chronically catheterized, non-anesthetized rats, leading to activation of second order neurons in the NTS as detected by c-Fos immunohistochemistry. Subsequent (double)-immunohistochemistry for either NMDA or AMPA glutamate receptors was used to determine the percentage of activated neurons expressing a particular receptor subtype. Gastric distension and duodenal nutrient stimuli produced slightly, but significantly different patterns of c-Fos induction in the dorsal vagal complex. Expression of NMDA receptors, as detected by a NR2ab subunit-specific antibody, was abundant throughout the dorsal medulla. The percentage of neurons in the NTS activated by gastric distension (63.9+/-2.9%), linoleic acid (62.8+/-1.4%), and glucose (64.1+/-1.4%), expressing NMDA receptor was similar. Expression of AMPA receptors, as detected by a GLUR2/3 subunit-specific antibody, was equally abundant throughout the dorsal medulla. Again, the percentage of activated neurons expressing GLUR2/3 was similar for the gastric distension (59.8-65.6%) and duodenal linoleic acid (60.6-67.0%) stimuli, and for the various subnuclei of the NTS. Finally, GLUR1-specific immunoreactivity was much less abundant, with only a small percentage of distension-activated (4.4+/-0.4%) and linoleic acid-activated (5.1+/-0.4%) neurons expressing this receptor subunit. The results suggest a widespread, general involvement of both NMDA and AMPA receptors in primary afferent signal transmission at the level of the NTS, with no differential recruitment of the examined receptor subtypes by the different gastrointestinal sensory stimuli. This may indicate a high degree of convergence among sensory signals, or alternatively, the presence of other transmission systems such as peptides referring sensory specificity to second order neurons.