Postsynaptic inhibition of hypoglossal motoneurons produces atonia of the genioglossal muscle during rapid eye movement sleep

Abstract

Study objectives: Hypoglossal motoneurons were recorded intracellularly to determine whether postsynaptic inhibition or disfacilitation was responsible for atonia of the lingual muscles during rapid eye movement (REM) sleep.

Design: Intracellular records were obtained of the action potentials and subthreshold membrane potential activity of antidromically identified hypoglossal motoneurons in cats during wakefulness, nonrapid eye movement (NREM) sleep, and REM sleep. A cuff electrode was placed around the hypoglossal nerve to antidromically activate hypoglossal motoneurons. The state-dependent changes in membrane potential, spontaneous discharge, postsynaptic potentials, and rheobase of hypoglossal motoneurons were determined.

Analyses and results: During quiet wakefulness and NREM sleep, hypoglossal motoneurons exhibited spontaneous repetitive discharge. In the transition from NREM sleep to REM sleep, repetitive discharge ceased and the membrane potential began to hyperpolarize; maximal hyperpolarization (10.5 mV) persisted throughout REM sleep. During REM sleep there was a significant increase in rheobase, which was accompanied by barrages of large-amplitude inhibitory postsynaptic potentials (IPSPs), which were reversed following the intracellular injection of chloride ions. The latter result indicates that they were mediated by glycine; IPSPs were not present during wakefulness or NREM sleep.

Conclusions: We conclude that hypoglossal motoneurons are postsynaptically inhibited during naturally occurring REM sleep; no evidence of disfacilitation was observed. The data also indicate that glycine receptor-mediated postsynaptic inhibition of hypoglossal motoneurons is crucial in promoting atonia of the lingual muscles during REM sleep.

Keywords: IPSP; OSA; REM sleep; atonia; hypoglossal; motoneuron; postsynaptic inhibition.

Figure 1

Positive identification of an intracellularly recorded hypoglossal motoneuron. (A) Superimposed traces of three consecutive trials of antidromic activation of the motoneruron. This representative hypoglossal motoneuron exhibited antidromically evoked action potentials with a constant latency following stimulation of the ipsilateral hypoglossal nerve (arrows) during naturally occurring wakefulness. (B) An example of a postspike after-hyperpolarizing potential is presented with an expanded time base. Hypoglossal nerve stimulus: 3.4 V (arrowheads) (A,B).

Figure 2

Hypoglossal motoneuron hyperpolarization during the transition from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep and throughout REM sleep. During the transition phase, only sporadic firing occurred. In contrast, during REM sleep, discharge ceased. The membrane potential (dashed line) returned to the same level as during NREM sleep when the animal awoke. Action potentials are truncated. PGO waves are indicated by dots above the LGN trace. EEG, electroencephalogram; EMG, electromyogram; EOG, electro-oculogram; LGN, lateral geniculate nucleus; PGO, pontogeniculo-occipital.

Figure 3

Example of the spontaneous discharge of a hypoglossal motoneuron during NREM sleep (A). At the onset of REM sleep, hyperpolarization occurred and discharge ceased, except momentarily in conjunction with REM sleep related phasic events (B) 60 sec intervened between panels A and B. Selected segments of traces in A and B as marked by brackets C and D are illustrated in the inset at an expanded time sweep.

Figure 4

Spontaneous, large-amplitude inhibitory postsynaptic potentials (IPSPs, recorded using a potassium citrate-filled microelectrode) were present only during the nonrapid eye movement (NREM)-rapid eye movement (REM) sleep transition and throughout REM sleep (asterisks) (B). They were absent during NREM sleep (A). When chloride ions were injected by steady current (-3.9 nA), the REM sleep-specific IPSPs were reversed in polarity (asterisks) (C). A and B are records from a representative motoneuron during NREM and REM sleep, respectively; both top and bottom traces in C are records from another motoneuron that was recorded with a chloride-filled electrode.

Figure 5

Examples of the increase in rheobase for motoneurons recorded during nonrapid eye movement (NREM) sleep (rheobase = 0.3 nA) (A) compared to that during rapid eye movement (REM) sleep (rheobase = 2 nA) (B). Top trace, intracellular potentials; bottom trace, current monitor.