A Review of the Pedunculopontine Nucleus in Parkinson's Disease

Abstract

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.

Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

“…The PPN is involved in arousal, motivation, and the organization of rapid eye movement (REM) sleep (42). The PPN has strong connections to the substantia nigra and has been implicated in REM sleep disorders associated with Parkinson's disease (43). The subcoeruleus nucleus in the rostral brainstem has also been implicated in the control of REM sleep in Parkinson's (44).…”

Motor Coordination Disorders Evaluated through the Grid Test and Changes in the Nigral Nrf2 mRNA Expression in Rats with Pedunculopontine Lesion

“…The analysis of the effects of neurotoxic injury of PPN on motor performance must take into account several essential aspects: (i) the multiple morpho–functional relationships of PPN with basal ganglia, the thalamus and the cerebral cortex [ 35 ]; (ii) the projections of the PPN to the spinal cord through the reticulospinal tract [ 35 , 36 ]).…”

“…The pontine neurons, which are part of the mesopontine segment, behave as a very important interface between the basal ganglia and the brain stem [ 35 ]. In this modulating role, they participate in the control of postural and limb muscle tone during voluntary movements associated with locomotion [ 35 ]. Our results suggest that PPN neurotoxic injury compromises the integrative function of this nucleus in the control of muscle tone in both the axial and distal muscles.…”

“…Although this variable did not reach statistical significance, we consider that its trend should be taken into account since it reinforces the criterion of dysfunction in motor coordination necessary for the execution of this behavioral paradigm. Considering the multiple morpho–functional relationships of the PPN with structures involved in motor control, from reference [ 35 ] we can hypothesize that the pontine injury causes the neural mechanisms that support postural control and ambulation to lose sensitivity and accuracy. This compromise might be more evident in the initial seconds after the experimental subject faces the challenge of wandering on the discontinuous elevated support surface.…”

Zona incerta as a therapeutic target in Parkinson’s disease

“…The MLR, which contains nuclei interconnected with the ZI (PPN, cuneiform nucleus), is a coordination centre for activation and control of spinal locomotor generator neurons [118,141,143]. The MLR is also connected with the basal ganglia, thalamus and other structures suggested to be involved in PD pathology [11,144], and neurons of the PPN has been found to be inhibited in animal models of PD [145,146]. What is interesting, the ZI is interconnected mainly with pars dissipata of the PPN, a subregion, which receives projections from the GPi and SNr, and contains bursting neurons (probably glutamatergic) involved in initiation of programmed movements [5].…”