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Noradrenergic modulation of masseter muscle activity during natural rapid eye movement sleep requires glutamatergic signalling at the trigeminal motor nucleus
Author(s) -
Schwarz Peter B.,
Mir Saba,
Peever John H.
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.272633
Subject(s) - ampa receptor , neuroscience , glutamatergic , excitatory postsynaptic potential , masseter muscle , brainstem , rapid eye movement sleep , glutamate receptor , chemistry , biology , medicine , eye movement , receptor , inhibitory postsynaptic potential , anatomy
Key points A principal role of noradrenaline is to potentiate motoneuron output in response to excitatory transmitter input. It is unknown if α‐1 noradrenoceptor activation is sufficient to independently trigger masseter muscle activity during natural waking and sleeping behaviour in the absence of excitatory (glutamatergic) input. Here, we use behavioural, neuropharmacological and electrophysiological techniques during rapid eye movement (REM) sleep to demonstrate that the excitatory effects of noradrenaline on motor output are lost in the absence of an endogenous glutamatergic drive. These findings may shed light on the unremarkable therapeutic outcomes of aminergic drugs in treating certain sleep motor disorders, particularly during REM sleep.Abstract Noradrenergic neurotransmission in the brainstem is closely coupled to changes in muscle activity across the sleep–wake cycle, and noradrenaline is considered to be a key excitatory neuromodulator that reinforces the arousal‐related stimulus on motoneurons to drive movement. However, it is unknown if α‐1 noradrenoceptor activation increases motoneuron responsiveness to excitatory glutamate (AMPA) receptor‐mediated inputs during natural behaviour. We studied the effects of noradrenaline on AMPA receptor‐mediated motor activity at the motoneuron level in freely behaving rats, particularly during rapid eye movement (REM) sleep, a period during which both AMPA receptor‐triggered muscle twitches and periods of muscle quiescence in which AMPA drive is silent are exhibited. Male rats were subjected to electromyography and electroencephalography recording to monitor sleep and waking behaviour. The implantation of a cannula into the trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle activity as an index of motoneuronal output. We found that endogenous excitation of both α‐1 noradrenoceptor and AMPA receptors during waking are coupled to motor activity; however, REM sleep exhibits an absence of endogenous α‐1 noradrenoceptor activity. Importantly, exogenous α‐1 noradrenoceptor stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor blockade and nor can it elevate muscle activity during quiet REM, a phase when endogenous AMPA receptor activity is subthreshold. We conclude that the presence of an endogenous glutamatergic drive is necessary for noradrenaline to trigger muscle activity at the level of the motoneuron in an animal behaving naturally.