| Summary: | In this thesis, I examined the inhibitory control of REM sleep motor activity using both a pharmacological rat model and a genetic mouse model. I characterized the role for GABA and glycine in mediating the REM-specific suppression of muscle activity as well as their involvement in regulating the phasic muscle twitches that punctuate this atonia. Based on four specific research objectives, the following conclusions were drawn:
1. REM atonia is not directly mediated by glycinergic or GABAA-mediated inhibition. These data refute the prevailing hypothesis that REM atonia is caused by glycinergic inhibition. These receptors are, however, important in the regulation of phasic muscle twitch activity.
2. GABAB receptors can modulate REM atonia but only when acting in concert with GABAA and glycine receptors. Blockade of all three receptor types results in a partial reversal of REM atonia, suggesting a functional interaction is occurring between these receptors during REM sleep.
3. The phasic glycinergic/GABAA-mediated inhibitory drive present in REM sleep regulates the temporal pattern of phasic twitch activity that is seen across this state. I hypothesize that this progressively decreasing inhibitory input counteracts a gradually increasing excitatory input to shape the temporal distribution of muscle twitches across REM sleep.
4. A loss of normal inhibitory function may play a causal role in the pathology of REM sleep behaviour disorder (RBD), the sleep disorder characterized by excessive motor activity in REM sleep.
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