Homeostatic regulation through GABA and acetylcholine muscarinic receptors of motor trigeminal neurons following sleep deprivation

Abstract

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 GABAA and GABAB 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 GABAARs was significantly higher after sleep deprivation (SD, ~65%) than sleep control (SC, ~32%) and that the luminance of the GABAAR fluorescence was significantly higher after SD than SC and sleep recovery (SR). Although, all Mo5 neurons were positively stained for GABABRs 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 GABAA, GABAB 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 prolonged waking and resulting increased susceptibility to muscle hypotonia or atonia along with sleep.

Homeostatic Changes in GABA and Acetylcholine Muscarinic Receptors on GABAergic Neurons in the Mesencephalic Reticular Formation following Sleep Deprivation

“…Following SD, the proportion and luminance of the AChM2Rs on the plasma membrane of the RFMes GAD+ neurons increased relative to SC, presumably due to prolonged activity of RFMes GABAergic neurons during enforced waking. The proportion and density of the AChM2Rs on GAD+ neurons returned to control level with SR, presumably due to less activity or inactivity of the GABAergic neurons following SR. Our results here are parallel to the increase in proportion and density of AChM2Rs seen on the membrane of the Mo5 neurons following SD with prolonged waking, when these neurons are also presumed to be active ( Toossi et al, 2017 ).…”

Arousal and sleep circuits

“…These results indicated that homeostatic bidirectional changes in GABA A Rs occur in arousal and sleep circuits as a function of their state selective activities. This same principle was found to apply to other wake-active cell groups, including BF ACh neurons [178], motor neurons [179], and excitatory cortical neurons [180].…”

Motor inactivity in hibernating frogs: Linking plasticity that stabilizes neuronal function to behavior in the natural environment

“…Can activity‐dependent processes interact with aspects of the organismal environment to constrain their expression? An appropriate amount of compensation during chronic inactivity is an interesting counterexample to rodents and humans because a loss of activity input to motoneurons may lead to overcompensation (D'Amico, Condliffe, Martins, Bennett, & Gorassini, ; Toossi, Cid‐Pellitero, & Jones, ) or under compensation (Alvarez, Bullinger, Titus, Nardelli, & Cope, ; Cormery, Beaumont, Csukly, & Gardiner, ; Rotterman, Nardelli, Cope, & Alvarez, ) that causes motor impairment. Perhaps hibernating animals may hold insights into the mechanisms by which compensatory plasticity can be regulated across time to stabilize motor performance after prolonged and variable bouts of inactivity.…”