The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state

Abstract

The mesencephalic reticular formation (MRF) mainly composed by the pedunculopontine and the cuneiform nuclei is involved in the control of several fundamental brain functions such as locomotion, rapid eye movement sleep and waking state. On the one hand, the role of MRF neurons in locomotion has been investigated for decades in different animal models, including in behaving nonhuman primate (NHP) using extracellular recordings. On the other hand, MRF neurons involved in the control of waking state have been consistently shown to constitute the cholinergic component of the reticular ascending system. However, a dual control of the locomotion and waking state by the same groups of neurons in NHP has never been demonstrated in NHP. Here, using microelectrode recordings in behaving NHP, we recorded 38 neurons in the MRF that were followed during transition between wakefulness (TWS) and sleep, i.e., until the emergence of sleep episodes characterized by typical cortical slow wave activity (SWA). We found that the MRF neurons, mainly located in the pedunculopontine nucleus region, modulated their activity during TWS with a decrease in firing rate during SWA. Of interest, we could follow some MRF neurons from locomotion to SWA and found that they also modulated their firing rate during locomotion and TWS. These new findings confirm the role of MRF neurons in both functions. They suggest that the MRF is an integration center that potentially allows to fine tune waking state and locomotor signals in order to establish an efficient locomotion.

Class II histone deacetylases require P/Q-type Ca2+ channels and CaMKII to maintain gamma oscillations in the pedunculopontine nucleus

“…Moreover, the presence of gamma band activity has been confirmed in the cortical EEG and PPN of the cat in vivo when the animal is active; 24 and in the region of the PPN in humans during stepping, but not at rest 29 . PPN neurons were found to fire at low frequencies ~10 Hz at rest, but the same neurons increased firing to gamma band frequencies when the animal woke up, or when the animal began walking on a treadmill 30 . That is, the same cells were involved in both arousal and motor control.…”

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

“…The descending dopaminergic projections to the PPN could also regulate other important functions such as cognition, sleep (Stefani et al, 2013; Karachi and Francois, 2017), modulation of visual inputs during locomotion (Lee et al, 2014), arousal state (Garcia-Rill et al, 2015a,b; Goetz et al, 2016b), motivation, and reward (Xiao et al, 2016; Yoo et al, 2017). How the descending dopaminergic input to the PPN influences these functions should be the subject of future research.…”

Role of Calcium Channels in Bipolar Disorder

“…Gamma band activity has been reported in the PPN of the mouse in vitro [86], in the REM sleep-induction region of the rat to which the PPN projects [87], in the cat in vivo [81], and in the region of the PPN in humans during stepping [88]. A recent study described firing patterns of neurons in the region of the PPN in the monkey trained to walk on a treadmill [89]. PPN neurons during standing fired at low rates but then fired at beta/gamma frequencies during locomotion.…”

“…That is, brainstem driving of gamma band activity during waking carries with it coherence across distant cortical regions, while driving of gamma band activity during REM sleep does not include coherence across distant regions [91,92]. Also, carbachol-induced REM sleep with cataplexy is characterized by decreased gamma band coherence in the cortex [89 93]. These results suggest that, a) brainstem centers drive gamma band activity that is manifested in the cortical EEG, b) during waking, brainstem-thalamic projections include coherence across regions, and c) during REM sleep, which is controlled by the subcoeruleus dorsalis (SubCD) region (lesion of this region eliminates REM sleep, while injection of carbachol induces REM sleep signs), drives cortical EEG rhythms without coherence.…”