Figure 4.

Hypothesis for how the α2 adrenergic agonist DEX could induce postural muscle atonia (and hence loss-of-righting reflex) by engaging the same brainstem circuitry that causes muscle atonia during REM sleep. (A) During wakefulness, motor neurons in the spinal cord release acetylcholine onto skeletal muscle to cause excitation and muscle activity. The motor neurons are commanded from the motor neocortex, but receive facilitatory and permissive (dis-inhibitory) neuromodulatory inputs from the noradrenergic locus coeruleus (LC) and orexinergic neurons in the lateral hypothalamus. (B) During REM sleep, a group of glutamatergic neurons in the pontine inhibitory area become active and drive GABAergic interneurons in the medullary inhibitory area to silence the noradrenergic neurons in the LC and also the motor neurons in the spinal cord—the net result is muscle atonia. (C) We hypothesize that DEX could activate α2a receptors, either on the soma or terminals of the noradrenergic LC neurons to inhibit noradrenaline (NA) release onto spinal motor neurons. This removes the permissive modulatory influence on motor neuron excitation. Not all the circuitry is shown, as it is not known which other cell types have the α2a receptors. Adapted and extended from McGregor and Siegel (2010); Blumberg (2013) and Zhang et al. (2015).