Differential distribution of 5HT2A and NMDA receptors in single cells within the rat medial nucleus of the solitary tract.

Activation of serotonin (5-hydroxytryptamine; 5HT) receptors of the 2A subtype (5HT2A) in the intermediate portion of the medial nucleus tractus solitarius (mNTS) produces marked hypotension and bradycardia. This portion of the mNTS receives major input from glutamatergic baroreceptor afferents. Thus, the cardiorespiratory effects of 5HT2A agonists may be attributed, in part, to interactions involving the glutamatergic target neurons, some of which express N-methyl-D-aspartate (NMDA) glutamate receptors. To determine the functional sites for activation of 5HT2A receptors and their relationship to NMDA receptors in this region, we used electron microscopic immunocytochemistry for the localization of antipeptide antisera selectively recognizing each receptor protein in the intermediate mNTS in rat brain. Of 1,052 5HT2A-labeled profiles, 38% were dendrites and dendritic spines, 27% were unmyelinated axons, 14% were axon terminals, and 11% were glial processes. These 5HT2A-labeled profiles frequently contained NR1 gold particles with dendrites comprising 68% of the total dual-labeled profiles. In dendrites, the 5HT2A immunoreactivity was localized to cytoplasmic organelles or discretely distributed on synaptic or extrasynaptic segments of the plasma membrane. In contrast, NR1 immunoreactivity was prominently localized to postsynaptic junctions and these were distinct from the 5HT2A receptor labeling when coexpressed in the same dendrites. Dendrites containing both receptors composed 56% (224/399) of the total 5HT2A-labeled dendrites and 34% (224/659) of the total NR1-labeled dendrites. Our results provide the first ultrastructural evidence that in the intermediate mNTS, 5HT2A receptor agonists may affect the postsynaptic excitability of many of the same neurons that show NMDA-evoked responses to glutamate.