Facilitation of saccade initiation by brainstem cholinergic system

Abstract

It is well known that the intermediate layer (SGI) of the mammalian superior colliculus (SC) receives cholinergic inputs originating from the pedunculopontine tegmental nucleus (PPTN). The action of the cholinergic input on the SGI neurons was investigated using whole-cell patch-clamp recording technique in slice preparations obtained from rats. Application of acetylcholine (ACh) induced fast inward currents mediated by nicotinic ACh receptors in the SGI neurons. Depolarization induced by nicotine enhanced the N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potential component and lowered the threshold of bursting response in the SGI neurons to stimulation of the superficial layer. Thus, the cholinergic input to the SGI facilitates the signal transmission through the direct visuomotor pathway in the SC. The behavioral correlate of this observation was explored by microinjection of nicotine into the SC of awake monkeys during visually guided saccade task; injection of nicotine increased frequency of express saccades, the saccades with extremely short reaction times (<120 ms). Analysis of single unit activity of the PPTN neurons revealed that a population of the PPTN neurons increased firing preceding saccades in a particular direction and also during the GAP period between the offset of fixation point and onset of the saccade target. Thus, PPTN neurons may be involved in execution and preparation of saccades. All these results explain the mechanisms of how the brainstem cholinergic system facilitates initiation of saccades presumably depending on attention or vigilance level of the animal.