Dichotomy between motor and cognitive functions of midbrain cholinergic neurons

Cholinergic neurons of the pedunculopontine nucleus (PPN) are interconnected with all the basal ganglia structures, as well as with motor centers in the brainstem and medulla. Recent theories put into question whether PPN cholinergic neurons form part of a locomotor region that directly regulates the motor output, and rather suggest a modulatory role in adaptive behavior involving both motor and cognitive functions. In support of this, experimental studies in animals suggest that cholinergic neurons reinforce actions by signaling reward prediction and shape adaptations in behavior during changes of environmental contingencies. This is further supported by clinical studies proposing that decreased cholinergic transmission originated in the PPN is associated with impaired sensorimotor integration and perseverant behavior, giving rise to some of the symptoms observed in Parkinson's disease and progressive supranuclear palsy. Altogether, the evidence suggests that cholinergic neurons of the PPN, mainly through their interactions with the basal ganglia, have a leading role in action control.