Noradrenaline triggers muscle tone by amplifying glutamate-driven excitation of somatic motoneurones in anaesthetized rats.
Postural muscle tone is potently suppressed during sleep and cataplexy. Since brainstem noradrenergic cell discharge activity is tightly coupled with state-dependent changes in muscle activity, it is assumed that noradrenergic drive on to somatic motoneurones modulates basal muscle tone. However, it has never been determined whether noradrenergic neurotransmission acts to directly regulate motoneurone activity or whether it functions to modulate prevailing synaptic activity. This is an important distinction because noradrenaline regulates cell excitability by both directly depolarizing neurones and by indirectly potentiating glutamate-mediated excitation. We used reverse-microdialysis, electrophysiology, neuro-pharmacological and histological techniques in anaesthetized rats to determine whether strengthening noradrenergic drive (via exogenous noradrenaline application) on to trigeminal motoneurones affects masseter muscle tone by increasing spontaneous motoneurone activity or whether it acts to amplify prevailing glutamate-driven excitation. Although noradrenaline is hypothesized to modulate motor activity, we found that direct stimulation of trigeminal motoneurones by alpha(1)-adrenoceptor activation had no direct effect on basal masseter tone. However, when glutamate-driven excitation was increased at the trigeminal motor pool by either endogenous glutamate release (induced by the monosynaptic masseteric reflex) or exogenous AMPA application, noradrenaline triggered a potent increase in basal masseter tone. The stimulatory effects of noradrenaline were unmasked and rapidly switched on only in the presence of glutamatergic transmission. Blockade of AMPA receptors abolished this excitatory effect, indicating that noradrenergic drive requires ongoing glutamatergic activity. Our data indicate that exogenous noradrenergic drive does not directly affect spontaneous motoneurone discharge activity in anaesthetized rats; rather, it triggers postural muscle tone by amplifying prevailing glutamate-driven excitation.
Department Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, Ontario, M5S 3G5, Canada.
Peter B
PB
Schwarz
Nicole
N
Yee
Saba
S
Mir
John H
JH
Peever
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D004576:Electromyography; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008406:Masseter Muscle / Q000294:innervation / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D014278:Trigeminal Nuclei / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D018091:Receptors, AMPA; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D017470:Receptors, Glutamate; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C041226:Terazosin; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin