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Revisiting Antagonist Effects in Hypoglossal Nucleus: Brainstem Circuit for the State-Dependent Control of Hypoglossal Motoneurons: A Hypothesis.

Fenik VB - Front Neurol (2015)

Bottom Line: We concluded that noradrenergic disfacilitation is the major mechanism that is responsible for approximately 90% of the depression of hypoglossal motoneurons, whereas the remaining 10% can be explained by serotonergic mechanisms that have net inhibitory effect on hypoglossal nerve activity during REM sleep-like state.We hypothesized that both noradrenergic and serotonergic state-dependent mechanisms indirectly control hypoglossal motoneuron excitability during REM sleep; their activities are integrated and mediated to hypoglossal motoneurons by reticular formation neurons.In addition, we proposed a brainstem neural circuit that can explain the new findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterans Affairs Greater Los Angeles Healthcare System , Los Angeles, CA , USA ; Websciences International , Los Angeles, CA , USA.

ABSTRACT
We reassessed and provided new insights into the findings that were obtained in our previous experiments that employed the injections of combined adrenergic, serotonergic, GABAergic, and glycinergic antagonists into the hypoglossal nucleus in order to pharmacologically abolish the depression of hypoglossal nerve activity that occurred during carbachol-induced rapid-eye-movement (REM) sleep-like state in anesthetized rats. We concluded that noradrenergic disfacilitation is the major mechanism that is responsible for approximately 90% of the depression of hypoglossal motoneurons, whereas the remaining 10% can be explained by serotonergic mechanisms that have net inhibitory effect on hypoglossal nerve activity during REM sleep-like state. We hypothesized that both noradrenergic and serotonergic state-dependent mechanisms indirectly control hypoglossal motoneuron excitability during REM sleep; their activities are integrated and mediated to hypoglossal motoneurons by reticular formation neurons. In addition, we proposed a brainstem neural circuit that can explain the new findings.

No MeSH data available.


Related in: MedlinePlus

The time-courses of spontaneous activity recorded in the hypoglossal nerve after injections of a mix containing both prazosin (Pz) and methysergide (Me) (open squares), prazosin only (filled circles) and methysergide only (filled triangles) into hypoglossal nucleus. Modified from Fenik et al. (35) with permission of the American Thoracic Society. Copyright © 2015 American Thoracic Society.
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Figure 3: The time-courses of spontaneous activity recorded in the hypoglossal nerve after injections of a mix containing both prazosin (Pz) and methysergide (Me) (open squares), prazosin only (filled circles) and methysergide only (filled triangles) into hypoglossal nucleus. Modified from Fenik et al. (35) with permission of the American Thoracic Society. Copyright © 2015 American Thoracic Society.

Mentions: Thus, it seems that prazosin is fully responsible for the disfacilitation, whereas methysergide for the disinhibitory effects on the REM-HD. The inhibitory role of 5HT in REM-HD is unexpected. However, this conclusion is additionally supported by the time-courses of the effects methysergide on the spontaneous activity in the hypoglossal nerve (Figure 3). During the diffusion, prazosin blocked more α1-adrenoceptors and more excitatory inputs to hypoglossal motoneurons were removed, which pushed the hypoglossal nerve activity down to its minimal level approximately at the time of the late carbachol responses (Figure 3, filled circles). The methysergide had less dramatic effects on the spontaneous nerve activity (Figure 3, filled triangles) that affected the time-course of combined antagonist effects (open squares). In addition, the time-course of methysergide effects had a bi-phasic shape. Initially, the spontaneous activity in hypoglossal nerve decreased likely due to the state-independent disfacilitation (see above), i.e., affecting receptors that likely do not contribute to REM-HD. However, at later times, hypoglossal nerve activity started to increase and reached its peak approximately at the time of the late carbachol responses (see Figure 3). This increase of hypoglossal nerve activity suggests that methysergide diffused to locations where it affected different 5HT receptors, so that its net effect was disinhibitory to hypoglossal motoneurons. We believe that these are the 5HT receptors, which mediate the depression of hypoglossal nerve activity in the “prazosin only” trials during the late carbachol-induced REMSLS (C2 in Figure 2D).


Revisiting Antagonist Effects in Hypoglossal Nucleus: Brainstem Circuit for the State-Dependent Control of Hypoglossal Motoneurons: A Hypothesis.

Fenik VB - Front Neurol (2015)

The time-courses of spontaneous activity recorded in the hypoglossal nerve after injections of a mix containing both prazosin (Pz) and methysergide (Me) (open squares), prazosin only (filled circles) and methysergide only (filled triangles) into hypoglossal nucleus. Modified from Fenik et al. (35) with permission of the American Thoracic Society. Copyright © 2015 American Thoracic Society.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664632&req=5

Figure 3: The time-courses of spontaneous activity recorded in the hypoglossal nerve after injections of a mix containing both prazosin (Pz) and methysergide (Me) (open squares), prazosin only (filled circles) and methysergide only (filled triangles) into hypoglossal nucleus. Modified from Fenik et al. (35) with permission of the American Thoracic Society. Copyright © 2015 American Thoracic Society.
Mentions: Thus, it seems that prazosin is fully responsible for the disfacilitation, whereas methysergide for the disinhibitory effects on the REM-HD. The inhibitory role of 5HT in REM-HD is unexpected. However, this conclusion is additionally supported by the time-courses of the effects methysergide on the spontaneous activity in the hypoglossal nerve (Figure 3). During the diffusion, prazosin blocked more α1-adrenoceptors and more excitatory inputs to hypoglossal motoneurons were removed, which pushed the hypoglossal nerve activity down to its minimal level approximately at the time of the late carbachol responses (Figure 3, filled circles). The methysergide had less dramatic effects on the spontaneous nerve activity (Figure 3, filled triangles) that affected the time-course of combined antagonist effects (open squares). In addition, the time-course of methysergide effects had a bi-phasic shape. Initially, the spontaneous activity in hypoglossal nerve decreased likely due to the state-independent disfacilitation (see above), i.e., affecting receptors that likely do not contribute to REM-HD. However, at later times, hypoglossal nerve activity started to increase and reached its peak approximately at the time of the late carbachol responses (see Figure 3). This increase of hypoglossal nerve activity suggests that methysergide diffused to locations where it affected different 5HT receptors, so that its net effect was disinhibitory to hypoglossal motoneurons. We believe that these are the 5HT receptors, which mediate the depression of hypoglossal nerve activity in the “prazosin only” trials during the late carbachol-induced REMSLS (C2 in Figure 2D).

Bottom Line: We concluded that noradrenergic disfacilitation is the major mechanism that is responsible for approximately 90% of the depression of hypoglossal motoneurons, whereas the remaining 10% can be explained by serotonergic mechanisms that have net inhibitory effect on hypoglossal nerve activity during REM sleep-like state.We hypothesized that both noradrenergic and serotonergic state-dependent mechanisms indirectly control hypoglossal motoneuron excitability during REM sleep; their activities are integrated and mediated to hypoglossal motoneurons by reticular formation neurons.In addition, we proposed a brainstem neural circuit that can explain the new findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterans Affairs Greater Los Angeles Healthcare System , Los Angeles, CA , USA ; Websciences International , Los Angeles, CA , USA.

ABSTRACT
We reassessed and provided new insights into the findings that were obtained in our previous experiments that employed the injections of combined adrenergic, serotonergic, GABAergic, and glycinergic antagonists into the hypoglossal nucleus in order to pharmacologically abolish the depression of hypoglossal nerve activity that occurred during carbachol-induced rapid-eye-movement (REM) sleep-like state in anesthetized rats. We concluded that noradrenergic disfacilitation is the major mechanism that is responsible for approximately 90% of the depression of hypoglossal motoneurons, whereas the remaining 10% can be explained by serotonergic mechanisms that have net inhibitory effect on hypoglossal nerve activity during REM sleep-like state. We hypothesized that both noradrenergic and serotonergic state-dependent mechanisms indirectly control hypoglossal motoneuron excitability during REM sleep; their activities are integrated and mediated to hypoglossal motoneurons by reticular formation neurons. In addition, we proposed a brainstem neural circuit that can explain the new findings.

No MeSH data available.


Related in: MedlinePlus