Distribution of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptor subunits on respiratory motor and premotor neurons in the rat

Glutamate is required for the transmission of inspiratory drive in respiratory premotor and motor neurons. The glutamate receptors (GluRs) responsible for this essential function have yet to be anatomically characterized. We mapped the GluR subtypes expressed by respiratory promotor and motor neurons by using combined immunohistochemistry and retrograde labeling in adult rats. Phrenic motoneurons and bulbospinal ventral respiratory group (VRG) neurons were retrogradely labeled and immunolabeled with subunit-specific antibodies against the N-methyl-D-aspartate (NMDA) receptor subtype (NMDAR1) and the non-NMDA receptor subtypes, α-amino-3- hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; GluR1, GluR2/3, GluR4) and kainate (GluRS-7). Phrenic motoneurons and bulbospinal VRG neurons showed positive immunolabeling for all five GluR subunits. These results support the hypothesis that NMDA and non-NMDA receptor subtypes underlie the excitation of bulbospinal VRG neurons and phrenic motoneurons. Furthermore, immunolabeling for each receptor subtype demonstrated a unique distribution along the neuronal membrane. Immunoreactivity for AMPA receptor subunits was distributed throughout somata and proximal dendrites, NMDAR1 subunit immunolabeling was localized to somata, and GluR5-7 subunit immunolabeling was confined largely to dendrites. The differential distribution of AMPA, kainate, and NMDA receptors on the somal and dendritic surface of respiratory neurons suggests that the location of glutamatergic synapses along the neuronal surface is an important determinant of glutamate-mediated postsynaptic currents. Consequently, different patterns of glutamatergic excitation of respiratory neurons could be achieved by selective activation of different profiles of GluR subtypes on different portions of the neuronal membrane.