| [Background]Changes in the excitability of the hypoglossal motor nuclei (HMN) in the medulla are responsible for alterations in tongue muscle activity across natural brain states such as wakefulness and sleep, and drug-induced states such as anesthesia. Since suppression of tongue muscle activity can predispose to airway narrowing and obstructions, which is important to the obstructive sleep apnea-hypopnea syndrome, OSAHS), it is of basic biological relevance to identify the neural mechanisms responsible for alterations in excitability of this hypoglossal motor pool. Nitric oxide (NO) is a freely diffusible intercellular signaling molecule, and there are projections of NO-synthesising neurons to hypoglossal motoneurons. Hypoglossal motoneurons also contain soluble guanylyl cyclase, the major cellular enzyme receptor for NO. Although NO has been proposed as a modulatory factor for several neuronal types in the central nervous system, its modulatory influence on hypoglossal motor activity remains to be elucidated in-vivo. Here we test the hypothesis that NO at the hypoglossal motor pool acts as an excitatory neurotransmitter.[Objective]To observe how NO (nitiic oxide) modulate the HMN (hypoglossal motor nuclei) and the modulation pathway in different brain states (anesthesia, wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep) as a neurotransmitter. [Methods]Two experimental preparations were used to test the effects of NO at the hypoglossal motor pool on genioglossus (GG) muscle activity:(1) Five groups of isoflurane-anesthetized, tracheotomized adult rats were first studied. Genioglossus and diaphragm muscle activities, blood pressure and the electroencephalogram were recorded. Microdialysis probes were implanted into the hypoglossal motor pool for delivery of increasing concentration of NO donor, NO scavenger, nitric oxide synthase (NOS) inhibitor, soluble guanylyl cyclase (sGC) inhibitor and constant concentration of mixture of NO donor and sGC inhibitor, respectively.(2) Rats were chronically implanted with genioglossus and diaphragm electrodes to record respiratory muscle activities and skull and neck muscle electrodes to record sleep wake states. Microdialysis guides were implanted above the hypoglossal motor pool, through which microdialysis probes were inserted into the motor pool on the day before the experiment. Recordings were conducted across all sleep-wake states during perfusion of NO donor and scarvenger, respectively.[Results](1) In the anesthetized rats:a. Application of the NO donor DEA at the hypoglossal motor nuclei increased respiratory-related genioglossus muscle activity. DEA at the HMN also activated tonic genioglossus activity but with statistically significant effects observed only at100mmol·L-1。b. Respiratory-related genioglossus muscle activity of those rats delivered NO scavenger, NOS inhibitor and sGC inhibitor decreased concentration-dependently.c. The sGC inhibitor elimilated the excitation effect of NO donor when they were delivered at the HMN together.(2) In the conscious rats:a. Application of the NO donor at the HMN increased tonic genioglossus muscle activity during NREM sleep but not in REM sleep and wakefulness. b. In contrast, NO scavenger at HMN has no effect on GG activity during each brain state.[Conclusion]These data suggest that(1) NO acts as an excitatory neurotransmitter at the hypoglossal motor pool.(2) NO is released locally of HMN and get effect through sGC-cGMP pathway.(3) The motor output responses (i.e., tonic vs. respiratory activation) are dependent upon the prevailing brain state (i.e., anesthesia vs. wakefulness NREM and REM sleep). NO increases respiratory-related genioglossus muscle activity in anesthetized rats. In NREM sleep of free-behavior rats, tonic genioglossus muscle activity can be increased by NO donor applied at HMN.
|
PDF Full Text Request