Sensory-motor gating and cognitive control by the brainstem cholinergic system

As an essential component of ascending activating systems, cholinergic neurons with diffuse projections are supposed to be involved in the regulation of cognitive processes such as attention, consciousness, learning, and memory. As for the role of cholinergic projections from the basal forebrain nuclei to cerebral cortical regions including hippocampus, a couple of models have been proposed that acetylcholine facilitates extrinsic inputs to the cortex and inhibits intracortical processing. In this review, to explore the possibility that there exists a generalized principle on the role of cholinergic systems in the brain, we summarized the knowledge so far obtained on the action of a brainstem cholinergic nucleus, the pedunculopontine tegmental nucleus (PPTN) at their target regions. By in vitro experiments we clarified that cholinergic inputs to the intermediate layer of the superior colliculus, presumably originating from the PPTN, facilitate generation of its motor outputs for the initiation of saccades. Furthermore, cholinergic inputs may enhance excitatory responses of mesopontine dopaminergic cells, for instance to reward-related signals. In addition, we observed that PPTN neurons showed multi-modal activities in behaving monkeys; their activities were related to execution and preparation of saccades, the level of task performance, and reward. The multi-modal activities encoded in the PPTN may suggest that PPTN associates movement-related activities with those related to task performance and reward. Together with the already reported facilitatory action on the sensory processing at the visual thalamus, these observations suggest that the brainstem cholinergic system facilitates the central processes for motor command generation and extrinsic sensory processing. For our final goal of exploring the general working principle of the cholinergic systems, further studies are needed to clarify the effects of the brainstem cholinergic system on the intrinsic processing in the brain.