A recent review considers in

A recent review considers in detail the reasons why these parameters are effective for inducing stepping [1], but will not be considered here. Briefly, beta/gamma oscillations in every PPN cell are mediated by high threshold, voltage-dependent N- and P/Q-type calcium channels [42]. We discovered that every cell in the PPN manifests beta/gamma frequency oscillations when depolarized using current ramps, but not when using current steps [42]. This is the only property shared by every PPN neuron, whether cholinergic, glutamatergic, or GABAergic. That is, ramping up current avoided the activation of potassium channels that would prevent the membrane from reaching the depolarized levels needed to activate the high threshold, voltage-dependent N- and P/Q-type calcium channels essential to beta/gamma frequency oscillations [42]. This property makes it necessary that PPN Manumycin A be ramped up to reach the depolarizing thresholds for voltage-dependent calcium channels that are typically located in the dendrites [43]. Fig. 2 illustrates the properties of PPN cells that require that stimuli be ramped up, instead of suddenly turned on, in order to induce intrinsic gamma band oscillations. Current steps failed to maintain depolarization of the membrane potential, probably due to potassium channel activation, while ramps slowly (~1s) depolarize the membrane potential to activate the high threshold calcium channels.
The role of the RAS in posture and locomotion The RAS is a phylogenetically conserved system that modulates fight-or-flight responses. During waking, man׳s ability to detect predator or prey is essential to survival. Under these circumstances, it is not surprising that the RAS can modulate muscle tone and locomotion. This system is thus intrinsically linked to the control of the motor system in order to optimize attack or escape. During REM sleep, the atonia keeps us from acting out our dreams. In fact, only our diaphragm and eye muscles appear to be acting out dream content. Therefore, during both waking and REM sleep, two states modulated by the PPN, the RAS can influence muscle tone and locomotion via the same reticulospinal systems [44]. For example, in a standing individual, there is tonic activation of anti-gravity, mainly extensor, muscles (the same ones inhibited in the atonia of REM sleep). Before the first step can be taken, there must be flexion of the leg, therefore, there must be a release from standing, or extensor inhibition, from this postural extensor bias. It should be noted that the first sign of stepping from a standing position will always be extensor inhibition to unlock the knees, only then followed by flexion. Extensor inhibition is thus the first action modulated by descending PPN outputs. The question is whether or not the extensor inhibition is prolonged to induce postural collapse (as in the cataplexy of narcolepsy), or does it lead to flexion–extension alternation and locomotion [44]. Outputs from the PPN and perhaps its descending target, the SubCoeruleus nucleus dorsali (SubCD), activate reticulospinal systems that lead to profound hyperpolarization of motoneurons, which is the mechanism responsible for the atonia of REM sleep [45]. Cholinergic projections from the PPN to the medioventral medulla elicit locomotion [46]. Outputs from this medullary region in turn activate reticulospinal systems that lead to the triggering of spinal pattern generators to induce stepping [37,38,47]. In general, electrical stimulation of the pontine and medullary reticular formation is known to induce decreased muscle tone at some sites, while producing stepping movements at other sites. This suggests the presence of a heterogeneous, distributed system of reticulospinal motor control. The required parameters of stimulation for eliciting these differing effects are important such that instantaneous, high frequency (>100Hz) trains (similar to high frequency bursting activity in the range of ponto-geniculo-occipital (PGO) burst neurons that may drive the atonia of REM sleep) trigger pathways which lead to decreased muscle tone, while lower frequency (40–60Hz) tonic stimulation leads gradually to the “recruitment” of locomotor movements [38,41]. Therefore, given the extensive evidence, it is to be expected that the PPN, as part of the RAS, should modulate both posture and locomotion in addition to arousal.