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GABA A receptor antagonism at the hypoglossal motor nucleus increases genioglossus muscle activity in NREM but not REM sleep
Author(s) -
Morrison Janna L.,
Sood Sandeep,
Liu Hattie,
Park Eileen,
Nolan Philip,
Horner Richard L.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00569.x
Subject(s) - non rapid eye movement sleep , genioglossus , sleep (system call) , neuroscience , gabaa receptor , medicine , hypoglossal nucleus , psychology , electromyography , nucleus , receptor , electroencephalography , computer science , operating system
The pharyngeal muscles, such as the genioglossus (GG) muscle of the tongue, are important for effective lung ventilation since they maintain an open airspace. Rapid‐eye‐movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity, even during strong reflex respiratory stimulation by elevated CO 2 . In vitro studies have demonstrated the presence of GABA A receptors on hypoglossal motoneurons, and these and other data have led to the speculation that GABA A mechanisms may contribute to the suppression of hypoglossal motor outflow to the GG muscle in REM sleep. We have developed an animal model that allows us to chronically manipulate neurotransmission at the hypoglossal motor nucleus using microdialysis across natural sleep‐wake states in rats. The present study tests the hypothesis that microdialysis perfusion of the GABA A receptor antagonist bicuculline into the hypoglossal motor nucleus will prevent the suppression of GG muscle activity in REM sleep during both room‐air and CO 2 ‐stimulated breathing. Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep‐wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) or 100 μ m bicuculline during room‐air and CO 2 ‐stimulated breathing (7 % inspired CO 2 ). GABA A receptor antagonism at the hypoglossal motor nucleus increased respiratory‐related GG activity during both room‐air ( P = 0.01) and CO 2 ‐stimulated breathing ( P = 0.007), indicating a background inhibitory GABA tone. However, the effects of bicuculline on GG activity depended on the prevailing sleep‐wake state ( P < 0.005), with bicuculline increasing GG activity in non‐REM (NREM) sleep and wakefulness both in room air and hypercapnia ( P < 0.01), but GG activity was effectively abolished in those REM periods without phasic twitches in the GG muscle. This abolition of GG activity in REM sleep occurred regardless of ACSF or bicuculline at the hypoglossal motor nucleus, or room‐air or CO 2 ‐stimulated breathing ( P > 0.63). We conclude that these data in freely behaving rats confirm previous in vitro studies that GABA A receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but the data also show that GABA A receptor antagonism at the hypoglossal motor nucleus does not increase GG muscle activity in natural REM sleep.