Reciprocal interaction between monoaminergic systems and the pedunculopontine nucleus: Implication in the mechanism of L-DOPA

The pedunculopontine nucleus (PPN) is part of the mesencephalic locomotor region (MLR) and has been involved in the control of gait, posture, locomotion, sleep, and arousal. It likely participates in some motor and non-motor symptoms of Parkinson's disease and is regularly proposed as a surgical target to ameliorate gait, posture and sleep disorders in Parkinsonian patients. The PPN overlaps with the monoaminergic systems including dopamine, serotonin and noradrenaline in the modulation of the above-mentioned functions. All these systems are involved in Parkinson's disease and the mechanism of the anti-Parkinsonian agents, mostly L-DOPA. This suggests that PPN interacts with monoaminergic neurons and vice versa. Some evidence indicates that the PPN sends cholinergic, glutamatergic and even gabaergic inputs to mesencephalic dopaminergic cells, with the data regarding serotonergic or noradrenergic cells being less well known. Similarly, the control exerted by the PPN on dopaminergic neurons, is multiple and complex, and more extensively explored than the other monoaminergic systems. The data on the influence of monoaminergic systems on PPN neuron activity are rather scarce. While there is evidence that the PPN influences the therapeutic response of L-DOPA, it is still difficult to discerne the reciprocal action of the PPN and monoaminergic systems in this action. Additional data are required to better understand the functional organization of monoaminergic inputs to the MLR including the PPN to get a clearer picture of their interaction.