title: Modulation of respiratory pattern and upper airway muscle activity by the pedunculopontine tegmentum: role of NMDA receptors.
abstract: The pedunculopontine tegmental nucleus (PPT) is postulated to have important functions relevant to the regulation of rapid eye movement (REM) sleep and arousal, and various motor control systems including respiration. We have recently shown that pharmacologic activation of a neuronal subpopulation within the PPT, induced by micropipette injection of glutamate in nanoliter volumes, can produce respiratory rhythm disturbances and changes in genioglossus muscle activity in anesthetized rats. The aim of this study was to determine whether the respiratory pattern disturbance and increased genioglossus muscle tone induced by glutamate injection within the PPT are mediated by activation of N-methyl-D-aspartate (NMDA) receptors within the PPT. Experiments were performed in eight adult male spontaneously breathing Sprague-Dawley rats anesthetized using nembutal. Respiratory movements were monitored by piezoelectric strain gauge. Three-barrel glass pipettes were used to pressure inject glutamate (as a probe for respiratory modulating sites), ketamine (an NMDA channel blocker), and oil-red dye (to aid in histological verification of the injection sites) within the PPT. Electroencephalograms were recorded from the sensorimotor cortex, the hippocampus, and the pons, contralateral to the injection site. Electromyograms (EMGs) were recorded from the genioglossus muscle. The typical response to glutamate injection within the PPT respiratory-modulating region was immediate apnea followed by tachypnea and increased genioglossal tonic activity. The noncompetitive NMDA receptor channel-antagonist ketamine, injected at the same site and in the same volume as glutamate (5 nl), blocked respiratory dysrhythmia and genioglossal EMG responses to subsequent glutamate injections. For the first time, the present results suggest that respiratory rhythm and upper airway muscle tone are controlled by the activation of pedunculopontine tegmental nucleus NMDA receptors.
authors.affiliation: Department of Medicine, University of Illinois, Chicago, IL, 60612, USA. jasnasap@uic.edu
authors.forename: Jasna
authors.initials: J
authors.lastname: Saponjic
authors.forename: Miodrag
authors.initials: M
authors.lastname: Radulovacki
authors.forename: David W
authors.initials: DW
authors.lastname: Carley
mesh_terms: D000818:Animals; D001931:Brain Mapping; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012891:Sleep Apnea Syndromes / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*; D014059:Tongue / Q000294:innervation* / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine