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

Victor B Fenik

doi:10.3389/fneur.2015.00254

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.

Highlights

The atonia of skeletal muscles is an insignia that distinguishes rapid-eye-movement (REM) sleep from the other two states of mammal existence, such as non-REM (NREM) sleep and wakefulness
This indicates that different neurotransmitters mediate REM-induced depression of muscle tone in different motoneurons. Those studies conclusively showed that [1] REM sleep-induced depression of spinal motoneurons is due to postsynaptic inhibition mediated by glycine [40] and [2] REM sleep-induced depression of hypoglossal motoneurons is due to withdrawal of noradrenergic and serotonergic drives [35]
We have conducted a series of experiments with a goal to determine the neurochemical mechanisms of the depression of hypoglossal motoneurons during REM sleep-like state (REMSLS) using a carbachol model of REM sleep in anesthetized rats [33,34,35]

Summary

INTRODUCTION

The atonia of skeletal muscles is an insignia that distinguishes rapid-eye-movement (REM) sleep from the other two states of mammal existence, such as non-REM (NREM) sleep and wakefulness. Iontophoretically applied strychnine, a glycinergic antagonist, abolished all important REM sleep-induced features that contribute to the motoneuron deactivation during REM sleep: [1] hyperpolarization of the motoneuron membrane that increases the threshold for the action potential generation; [2] decrease in input resistance that shunted summation of sub-threshold excitatory postsynaptic potentials; and [3] the increase in rheobase that is a principal measure of neuronal excitability Since both membrane hyperpolarization and increase in membrane conductance contribute to increase in rheobase, the abolition of the REM sleep-related increase in rheobase by strychnine is the major finding obtained in this study indicating that the reduction of excitability of lumbar motoneurons is due to postsynaptic inhibition mediated by glycine. The effectiveness of this antagonism was more pronounced during REM sleep, which suggested that postsynaptic cholinergic inhibition may contribute to REM-HD [66]

Conclusion

Findings

CONCLUSION