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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

A hypothetical brainstem circuit that illustrates the key neuronal pools, which participate in the state-dependent control of hypoglossal motoneuron excitability during REM sleep. The reticular formation neurons (RF-neurons) integrate and mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. The REM-OFF A7 noradrenergic neurons excite RF-neurons via α1-adrenoceptors. The RF-neurons are tonically inhibited by local GABAergic neurons, activity of which is controlled by REM-OFF raphe serotonergic neurons via inhibitory 5HT1 receptors. The mediators and receptors through which RF-neurons directly or indirectly excite hypoglossal motoneurons remain to be determined. A hypothetical REM-ON excitatory drives to hypoglossal and/or RF-neurons are controlled by GABAA inhibitory receptors. The curved line shows the extent of the diffusion of antagonists that were injected into hypoglossal nucleus as discussed in this review.
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Figure 4: A hypothetical brainstem circuit that illustrates the key neuronal pools, which participate in the state-dependent control of hypoglossal motoneuron excitability during REM sleep. The reticular formation neurons (RF-neurons) integrate and mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. The REM-OFF A7 noradrenergic neurons excite RF-neurons via α1-adrenoceptors. The RF-neurons are tonically inhibited by local GABAergic neurons, activity of which is controlled by REM-OFF raphe serotonergic neurons via inhibitory 5HT1 receptors. The mediators and receptors through which RF-neurons directly or indirectly excite hypoglossal motoneurons remain to be determined. A hypothetical REM-ON excitatory drives to hypoglossal and/or RF-neurons are controlled by GABAA inhibitory receptors. The curved line shows the extent of the diffusion of antagonists that were injected into hypoglossal nucleus as discussed in this review.

Mentions: The Figure 4 shows the suggested neural circuit. The major neuronal pools that are responsible for the state-dependent control of hypoglossal motoneurons are noradrenergic A7 neurons and hypothetical medullary reticular formation neurons (RF-neurons) that mediate the noradrenergic excitatory drive from A7 neurons to hypoglossal motoneurons (72). We propose that the A7 neurons excite the RF-neurons by activating their α1-adrenoceptors, which are located within the radius of the diffusion of the antagonists (see Figure 4) that was estimated 0.9–1.4 mm from the center of the hypoglossal nucleus (34). These RF-neurons have a net excitatory effect on hypoglossal motoneurons, but their projections to hypoglossal motoneurons (direct or indirect) and the involved neurotransmitters/receptors need to be determined in future experiments. The A7 neurons decrease their activity during REMSLS (73) and are likely to be silent during REM sleep (74). Therefore, the silencing of A7 neurons during REM sleep disfacilitates the RF-neurons and, thereby, hypoglossal motoneurons. Our hypothesis that aminergic drive affects hypoglossal motoneurons indirectly, i.e., mediated by RF-neurons, is in accordance with intracellular studies, in which no evidence for aminergic disfacilitation was found in hypoglossal motoneurons during REM sleep or REMSLS (56, 58).


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

Fenik VB - Front Neurol (2015)

A hypothetical brainstem circuit that illustrates the key neuronal pools, which participate in the state-dependent control of hypoglossal motoneuron excitability during REM sleep. The reticular formation neurons (RF-neurons) integrate and mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. The REM-OFF A7 noradrenergic neurons excite RF-neurons via α1-adrenoceptors. The RF-neurons are tonically inhibited by local GABAergic neurons, activity of which is controlled by REM-OFF raphe serotonergic neurons via inhibitory 5HT1 receptors. The mediators and receptors through which RF-neurons directly or indirectly excite hypoglossal motoneurons remain to be determined. A hypothetical REM-ON excitatory drives to hypoglossal and/or RF-neurons are controlled by GABAA inhibitory receptors. The curved line shows the extent of the diffusion of antagonists that were injected into hypoglossal nucleus as discussed in this review.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: A hypothetical brainstem circuit that illustrates the key neuronal pools, which participate in the state-dependent control of hypoglossal motoneuron excitability during REM sleep. The reticular formation neurons (RF-neurons) integrate and mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. The REM-OFF A7 noradrenergic neurons excite RF-neurons via α1-adrenoceptors. The RF-neurons are tonically inhibited by local GABAergic neurons, activity of which is controlled by REM-OFF raphe serotonergic neurons via inhibitory 5HT1 receptors. The mediators and receptors through which RF-neurons directly or indirectly excite hypoglossal motoneurons remain to be determined. A hypothetical REM-ON excitatory drives to hypoglossal and/or RF-neurons are controlled by GABAA inhibitory receptors. The curved line shows the extent of the diffusion of antagonists that were injected into hypoglossal nucleus as discussed in this review.
Mentions: The Figure 4 shows the suggested neural circuit. The major neuronal pools that are responsible for the state-dependent control of hypoglossal motoneurons are noradrenergic A7 neurons and hypothetical medullary reticular formation neurons (RF-neurons) that mediate the noradrenergic excitatory drive from A7 neurons to hypoglossal motoneurons (72). We propose that the A7 neurons excite the RF-neurons by activating their α1-adrenoceptors, which are located within the radius of the diffusion of the antagonists (see Figure 4) that was estimated 0.9–1.4 mm from the center of the hypoglossal nucleus (34). These RF-neurons have a net excitatory effect on hypoglossal motoneurons, but their projections to hypoglossal motoneurons (direct or indirect) and the involved neurotransmitters/receptors need to be determined in future experiments. The A7 neurons decrease their activity during REMSLS (73) and are likely to be silent during REM sleep (74). Therefore, the silencing of A7 neurons during REM sleep disfacilitates the RF-neurons and, thereby, hypoglossal motoneurons. Our hypothesis that aminergic drive affects hypoglossal motoneurons indirectly, i.e., mediated by RF-neurons, is in accordance with intracellular studies, in which no evidence for aminergic disfacilitation was found in hypoglossal motoneurons during REM sleep or REMSLS (56, 58).

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