Introduction obstructive sleep apnea syndrome [32]. In an attempt to
Brain Research 885 2000 262–272 www.elsevier.com locate bres
Research report
Changes in electrophysiological properties of cat hypoglossal motoneurons during carbachol-induced motor inhibition
Simon J. Fung , Jack Yamuy, Ming-Chu Xi, John K. Engelhardt, Francisco R. Morales, Michael H. Chase
Department of Physiology and the Brain Research Institute , UCLA School of Medicine, 53-263 CHS, Los Angeles, CA 90095, USA
Accepted 12 September 2000
Abstract
The control of hypoglossal motoneurons during sleep is important from a basic science perspective as well as to understand the bases for pharyngeal occlusion which results in the obstructive sleep apnea syndrome. In the present work, we used intracellular recording
techniques to determine changes in membrane properties in adult cats in which atonia was produced by the injection of carbachol into the pontine tegmentum AS-carbachol. During AS-carbachol, 86 of the recorded hypoglossal motoneurons were found to be postsynapti-
cally inhibited on the basis of analyses of their electrical properties; the electrical properties of the remaining 14 were similar to motoneurons recorded during control conditions. Those cells that exhibited changes in their electrical properties during AS-carbachol also
displayed large-amplitude inhibitory synaptic potentials. Following sciatic nerve stimulation, hypoglossal motoneurons which responded with a depolarizing potential during control conditions exhibited a hyperpolarizing potential during AS-carbachol. Both spontaneous and
evoked inhibitory potentials recorded during AS-carbachol were comparable to those that have been previously observed in trigeminal and spinal cord motoneurons under similar experimental conditions as well as during naturally occurring active sleep. Calculations based on
modeling the changes that we found in input resistance and membrane time constant with a three-compartment neuron model suggest that shunts are present in all three compartments of the hypoglossal motoneuron model. Taken together, these data indicate that postsynaptic
inhibitory drives are widely distributed on the soma-dendritic tree of hypoglossal motoneurons during AS-carbachol. These postsynaptic inhibitory actions are likely to be involved in the pathophysiology of obstructive sleep apnea.
2000 Elsevier Science B.V. All rights
reserved.
Theme : Motor systems and sensorimotor integration
Topic : Spinal cord and brainstem
Keywords : Postsynaptic inhibition; Dendritic inhibition; REM sleep; Apnea
1. Introduction obstructive sleep apnea syndrome [32]. In an attempt to
understand the mechanism responsible for the reduction in Obstructive sleep apnea occurs because of a narrowing
motoneuron activity during AS, hypoglossal nerve record- of the upper airway which is due, in part, to a decrease in
ings were obtained during the suppression of motoneuron the activity of the tongue and laryngeal dilator muscles;
activity that occurs following the pontine injection of this sleep disorder arises during quiet NREM sleep and
carbachol; it was concluded that the activity of hypoglossal becomes exacerbated during active sleep AS; also called
motoneurons is reduced under these conditions [17,20]. It REM sleep [23]. Electromyographic studies suggest that
has been hypothesized that a disfacilitory mechanism is hypoglossal motoneurons innervating the tongue muscles
responsible for the carbachol-induced suppression in hypo- are less active during AS than during quiet sleep in both
glossal nerve activity because serotonin levels were found healthy subjects [33] and in patients diagnosed with
to be reduced in this motor nucleus [21] and the pre-motor serotonergic raphe neurons also reduced their firing under
these conditions [41]. However, when the endogenous
Corresponding author. Tel.: 11-310-825-3348. E-mail address
: sjfungucla.edu S.J. Fung.
effects of serotonin are blocked, there is still suppression
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 5 5 - 3
S .J. Fung et al. Brain Research 885 2000 262 –272
263
of hypoglossal motoneurons [22]. Therefore, other pro- Halothane was then discontinued and the anesthesia was
cesses, specifically postsynaptic inhibition, must play a key maintained using a-chloralose initial dose: 60 mg kg, i.v.,
role in the suppression of hypoglossal motoneurons during supplemental dose: 20 mg kg, i.v. throughout the rest of
AS-carbachol and consequently may also be involved in the experiment. Gallamine triethiodide Flaxedil , 1–2
the pathophysiology of the obstructive sleep apnea mg kg, i.v. was employed to improve stability during
syndrome. intracellular recording. Arterial blood pressure mean5120
The presence of AS-specific glycinergic postsynaptic mm Hg, end-tidal carbon dioxide 3.5–5 and core
inhibition in trigeminal and spinal motoneurons has been temperature 37.5–38.58C were monitored continuously.
shown in intracellular studies carried out in chronically- implanted, freely-behaving cats [8,24,29], which explains
2.2. Recording, stimulation and data analysis the suppression of the somatomotor reflex during AS
[7,15]. In addition postsynaptic inhibition of somatic Intracellular recordings from hypoglossal motoneurons
motoneurons with concurrent motor suppression has been were obtained using glass microelectrodes filled with a
observed in a pharmacological cholinergic model of AS solution of either 3 M KCl or 2 M K-citrate; tip resistance
following carbachol microinjection in the nucleus pontis ranged between 10 and 35 MV. Intracellular current
oralis NPO in both decerebrate [27] and a-chloralose injections were carried out through the recording mi-
anesthetized cats [19,42]. We have designated this active croelectrode by using an Axoclamp 2A preamplifier Axon
sleep-like state as AS-carbachol [44]. Instruments, Inc. operating in current clamp mode. The
In a preliminary report based upon intracellular record- reference electrode consisted of an Ag AgCl wire that was
ing techniques, we presented an overview of changes in wrapped with saline-soaked gauze and placed subcuta-
membrane properties of hypoglossal motoneurons during neously. The low-gain 103 and high-gain 1003 DC
AS-carbachol in decerebrate and a-chloralose anesthetized outputs of the preamplifier were monitored on an oscillos-
cats [43]. In the present work, we present complete, cope and stored on a video cassette recorder using a PCM
rigorous analyses of these data within the framework of adapter. The intracellular data were digitized off-line at 10
linear cable theory using a three-compartment electrical ms bin for action potentials and at 50 ms bin for signals
network neuron model. These data lead us to conclude that used to measure other membrane properties.
hypoglossal motoneurons are subjected to postsynaptic Hypoglossal motoneurons were identified by antidromic
inhibition during AS-carbachol and that these inhibitory activation via stimulating either the ipsilateral hypoglossal
processes are directed both to the soma and dendrites of nerve or its branches single rectangular pulses, 150 ms
hypoglossal motoneurons. duration, 2–7 V intensity. The antidromic spike amplitude
was measured from the baseline membrane potential to the peak of the spike. The resting membrane potential was