NMDA RECEPTORS CONTRIBUTE TO PRIMARY VISCERAL AFFERENT TRANSMISSION IN THE NUCLEUS OF THE SOLITARY TRACT

The nucleus of the solitary tract (NTS) is a principal site for coordi nating the reflex control of autonomic function. The nucleus receives and organizes primary visceral (sensory) afferent inputs from the grea t vessels, heart, lung, and gastrointestinal organs. Glutamate, the ex citatory neurotransmitter released by the primary afferent fibers, act ivates non-N-methyl-D-aspartate (non-NMDA) receptors on second-order n eurons in the NTS. Still in question is whether NMDA receptors on the second-order neurons are also activated. Accordingly, the purpose of t his study was to directly determine whether NMDA receptors contribute to synaptic transmission of primary visceral afferent input to second- order neurons in the NTS. Whole cell patch-clamp recordings were obtai ned from intermediate and caudal NTS neurons in rat coronal medullary slices. Excitatory postsynaptic currents (EPSCs) were evoked by stimul ation of the solitary tract (1-25 V, 0.1 ms, 0.2 or 0.5 Hz) at membran e potentials ranging from -90 to +60 mV. In 28 of 32 neurons in which current-voltage relationships were obtained for solitary-tract-evoked EPSCs, the currents had short onset latencies (3.42 +/- 1.03 ms, mean +/- SD), indicating that they were the result of monosynaptic activati on of second-order neurons. Solitary-tract-evoked EPSCs had both a fas t and a slow component. The amplitude of the slow component was nonlin early related to voltage (being revealed only at membrane potentials p ositive to -45 mV), blocked by the NMDA receptor antagonist DL-2-amino -5-monophosphovaleric acid (APV, 50 mu M; n = 12; P = 0.0001), and enh anced in nominally Mg2+-free perfusate at membrane potentials negative to -45 mV (n = 5; P = 0.016), demonstrating that the slow component w as mediated by NMDA receptors. The amplitude of the fast component was linearly related to voltage and blocked by the non-NMDA receptor anta gonist 2,3- dihydroxy-6-nitro-7-sulfamoylbenzo (F)quinoxaline (NBQX, 3 mu M; n = 9; P = 0.0014), demonstrating that the fast component was m ediated by non-NMDA receptors. The slow component of the EPSCs was not blocked by NBQX (n = 6; P = 0.134), nor was the fast component blocke d by APV (n = 12; P = 0.124). These results show that both NMDA and no n-NMDA receptors coexist on the same second-order NTS neurons and medi ate primary visceral afferent transmission in the NTS. The participati on of NMDA receptors suggests that second-order neurons in the NTS may have previously unrecognized integrative capabilities in the reflex c ontrol of autonomic function.