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The Journal of Neuroscience, February 15, 2003, 23(4):1548

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: An In Vivo Microdialysis Study

Tohro Kodama^{1, 2}, Yuan-Yang Lai², and Jerome M. Siegel²

¹ Department of Psychology, Tokyo Metropolitan Institute of Neuroscience, Fuchu, Tokyo 183 8526, Japan, and ² Department of Psychiatry, School of Medicine, University of California, Los Angeles, and Sepulveda Veterans Affairs Medical Center, North Hills, California 91343

We hypothesized that cessation of brainstem monoaminergic systems and an activation of brainstem inhibitory systems are both involved in pontine inhibitory area (PIA) stimulation-induced muscle atonia. In our previous study (Lai et al., 2001), we found a decrease in norepinephrine and serotonin release in motoneuron pools during PIA stimulation-induced muscle tone suppression. We now demonstrate an increase in inhibitory amino acid release in motor nuclei during PIA stimulation in the decerebrate cat using in vivo microdialysis and HPLC analysis techniques. Microinjection of acetylcholine into the PIA elicited muscle atonia and simultaneously produced a significant increase in both glycine and GABA release in both the hypoglossal nucleus and the lumbar ventral horn. Glycine release increased by 74% in the hypoglossal nucleus and 50% in the spinal cord. GABA release increased by 31% in the hypoglossal nucleus and 64% in the spinal cord during atonia induced by cholinergic stimulation of the PIA. As with cholinergic stimulation, 300 msec train electrical stimulation of the PIA elicited a significant increase in glycine release in the hypoglossal nucleus and ventral horn. GABA release was significantly increased in the hypoglossal nucleus but not in the spinal cord during electrical stimulation of the PIA. Glutamate release in the motor nuclei was not significantly altered during atonia induced by electrical or acetylcholine stimulation of the PIA. We suggest that both glycine and GABA play important roles in the regulation of upper airway and postural muscle tone. A combination of decreased monoamine and increased inhibitory amino acid release in motoneuron pools causes PIA-induced atonia and may be involved in atonia linked to rapid eye-movement sleep.

Key words: glycine; GABA; hypoglossal nucleus; spinal cord; upper airway; REM sleep; obstructive sleep apnea

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2341548-07$05.00/0

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