Early Phase of Pupil Dilation is Mediated by the Peripheral Parasympathetic Pathway

Pupil diameter fluctuates in association with changes in brain states induced by the neuromodulator systems. However, it remains unclear how the neuromodulator systems control the activity of the iris sphincter (constrictor) and dilator muscles to change the pupil size. The present study compared temporal patterns of pupil dilation during movement when each muscle was pharmacologically manipulated in the human eye. When the iris sphincter muscle was blocked with tropicamide, the latency of pupil dilation was delayed and the magnitude of pupil dilation was reduced during movement. In contrast, when the iris dilator muscle was continuously stimulated with phenylephrine, the latency and magnitude of rapid pupil dilation did not differ from the untreated control eye, but sustained pupil dilation was reduced until the end of movement. These results suggest that the iris sphincter muscle, which is under the control of the parasympathetic pathway, is quickly modulated by the neuromodulator system and plays a major role in rapid pupil dilation. However, the iris dilator muscle receives signals from the neuromodulator system with a slow latency and is involved in maintaining sustained pupil dilation. By pharmacologically manipulating the pupil dilator and constrictor muscles of human eye separately, we found that the pupil constrictor muscle is a primary controller of rapid pupil dilation upon brain arousal. However, the pupil dilator muscle, which is innervated by the sympathetic nervous system and is generally considered as a major regulator of pupil dilation, is not involved in rapid pupil dilation, but was involved in long-lasting pupil dilation.