Respiratory activation of the genioglossus muscle involves both non-NMDA and NMDA glutamate receptors at the hypoglossal motor nucleus in vivo

• Published in: Neuroscience Vol. 138; no. 4; pp. 1407 - 1424
• Main Authors: Steenland, H.W., Liu, H., Sood, S., Liu, X., Horner, R.L.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Animals; Biological and medical sciences; Excitatory Amino Acid Antagonists - pharmacology; Extracellular Fluid - drug effects; Extracellular Fluid - metabolism; Fundamental and applied biological sciences. Psychology; genioglossus muscle; glutamate; Glutamic Acid - metabolism; hypoglossal motor nucleus; Hypoglossal Nerve - drug effects; Hypoglossal Nerve - physiology; Male; medulla; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Microdialysis; Microinjections; Motor Neurons - drug effects; Motor Neurons - physiology; Muscle, Skeletal - innervation; Muscle, Skeletal - physiology; pharyngeal muscles; Rats; Reaction Time - drug effects; Reaction Time - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; respiratory control; Respiratory Physiological Phenomena - drug effects; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tongue - innervation; Vagotomy; Vagus Nerve - surgery; Vagus Nerve Injuries; Vertebrates: nervous system and sense organs; respiratory control; medulla; GG; AMPA; EEG; pharyngeal muscles; hypoglossal motor nucleus; d-APV; HMN; ACSF; CNQX; genioglossus muscle; NMDA; glutamate; EMG; Central nervous system; Motor nucleus; Glutamate receptor; Glutamate; Hypoglossal nucleus; Respiratory system; Encephalon; Respiratory muscle; Excitatory aminoacid; Neurotransmitter; NMDA receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.12.040

Brainstem respiratory neurons innervate the hypoglossal motor nucleus which in turn transmits this respiratory drive signal to the genioglossus muscle of the tongue. The mechanism of this transmission is important to help maintain an open airspace for effective breathing, and is thought to rely almost exclusively on non-N-methyl-d-aspartate (non-NMDA) glutamate receptor activation during respiration. However those studies were performed in slices of medulla from neonatal animals in vitro which may have led to an underestimation of the contribution of NMDA glutamate receptors that may normally operate in intact preparations. The current study tests the hypothesis that both NMDA and non-NMDA receptors contribute to respiratory drive transmission at the hypoglossal motor nucleus in vivo. Experiments were performed in urethane-anesthetized and tracheotomized adult Wistar rats in which vagus nerves were either intact or sectioned. In the presence of augmented genioglossus activity produced by vagotomy, microdialysis perfusion of either an NMDA receptor antagonist (d-2-amino-5-phosphonovaleric acid, 0.001–10mM) or a non-NMDA receptor antagonist (6-cyano-7-nitroquinoxaline-2, 3-dione disodium salt, 0.001–1mM) to the hypoglossal motor nucleus reduced respiratory-related genioglossus activity in a dose-dependent manner (P<0.001) indicating that both NMDA and non-NMDA glutamate receptors are necessary for transmission of the respiratory drive signal to genioglossus muscle in vivo. Similar effects were observed in the vagus nerve intact rats. Further experiments demonstrated that each delivered antagonist had effects that were specific to its respective receptor. Regression analysis also revealed that the activity of both NMDA and non-NMDA receptors at the hypoglossal motor nucleus is related to levels of the prevailing respiratory drive. These results show that both NMDA and non-NMDA glutamate receptors at the hypoglossal motor nucleus are involved in transmission of the respiratory drive signal to genioglossus muscle in vivo.