Homeostatic regulation through GABA and acetylcholine muscarinic receptors of motor trigeminal neurons following sleep deprivation (original) (raw)

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Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABA A and GABA B receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking. By immunofluorescence, we assessed that the proportion of Mo5 neurons positively stained for GABA A Rs was significantly higher after sleep deprivation (SD, ~65%) than sleep control (SC, ~32%) and that the luminance of the GABA A R fluorescence was significantly higher after SD than SC and sleep recovery (SR). Although, all Mo5 neurons were positively stained for GABA B Rs and AChM2Rs (100%) in all groups, the luminance of these receptors was significantly higher following SD as compared to SC and SR. We conclude that the density of GABA A , GABA B and AChM2 receptors increases on Mo5 neurons during SD. The increase in these receptors would be associated with increased inhibition in the presence of GABA and ACh and thus a homeostatic down-scaling in the excitability of the Mo5 neurons after in both masseter and genioglossus muscles (Soja et al. 1987;Brooks and Peever 2008;Morrison et al. 2003). In the genioglossus muscles, it was discovered that the muscle atonia during REMS could be selectively prevented by antagonism of acetylcholine (ACh) muscarinic (M) receptors using scopolamine or by blocking the inhibitory pathway through the G-protein coupled inwardly rectifying potassium channel (GIRK) to which the AChM2R is linked (Grace et al. 2013a, b). Given the demonstrated post-synaptic inhibitory action of the AChM2R through GIRK channels in motor neurons (Chevallier et al. 2006;Miles et al. 2007;Zhu et al. 2016), the demonstrated presence of ACh-M2Rs on Mo5 neurons (Hellstrom et al. 2003;Brischoux et al. 2008) and the established role of ACh in PS or REMS (Jones 1991), it would appear that such AChM2R-mediated inhibition could well occur during REMS. These results indicate that motor neurons in the brainstem, including the Mo5 neurons, are inhibited during sleep by both ionotropic glycine/GABA receptors and metabotropic GABA B and AChM2 receptors.