Activation of NMDA receptors is necessary for fast information transfer at brainstem vagal motoneurons.
The involvement of N-methyl-D-aspartate (NMDA) excitatory amino acid subtype receptors in synaptically driven excitatory responses of ambigual motoneurons was investigated in vivo and in vitro. In urethane-anaesthetized rats, fictive oesophageal peristalsis evoked by topical application of muscarine (0.05-0.5 nmol) to the dorsal surface of the solitarial complex (NTS) was reversibly blocked by ipsilateral intraambigual injection of DL-2-amino-7-phosphonoheptanoic acid (AP-7, 0.5-1.5 nM) and (+-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 0.5-1.5 nM). In brainstem sagittal slices, post-synaptic potentials were recorded from neurons of the compact formation of the nucleus ambiguus (AMBc). Stimulation of presumptive NTS afferents elicited a complex excitatory postsynaptic potential (EPSP) which usually consisted of both a high-threshold fast (HTF) and a low-threshold slow (LTS) component. Bath perfusion with AP-7 (30-50 microM) and CPP (50 microM) selectively blocked the HTF without affecting the LTS component, while kynurenate (1 mM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) nonselectively suppressed both components. With sufficient stimulus strength, the EPSP generated a single spike arising from the HTF component. AP-7 (50 microM) either blocked the spike or increased the firing threshold. Furthermore, at the resting membrane potential, bath-applied NMDA induced a net inward current (269 +/- 189 pA) which had a negative slope in the range of -95 to -35 mV. In conclusion, NMDA receptors participate in solitario-ambigual synaptic transmission under physiological conditions and activation of these receptors is necessary for functional information transfer in this pathway.
Wang
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Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Bieger
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D
Neuman
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000200:Action Potentials / Q000502:physiology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D006651:Histocytochemistry; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D000596:Amino Acids; D010879:Piperazines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C031231:2-amino-7-phosphonoheptanoic acid