The long-term objectives of this study are to understand the mechanisms underlying the neural control of the pupil in primates. In particular, experiments are proposed that will investigate the anatomy and physiology of the pupillary light reflex (PLR). When light is shone in one eye, there is a pupilloconstriction in that eye, and in the fellow eye. The former response is known as the direct pupillary light reflex, while the latter response is known as the consensual pupillary light reflex. In addition, when a near object is viewed, convergence and accommodation are accompanied by a pupilloconstriction - the pupillary near response. Despite a long history of research on the neural control of the pupil, few modern studies have investigated it in primates. Thus, the anatomy and the physiology of these clinically important reflexes are not well understood in primates. Studies of these reflexes in alert, trained primates are important for two reasons. First, they will provide much needed information on the neural control of the internal musculature of the eye by the central nervous system. Second, the pupillary reflexes described above are extremely useful to a clinician in diagnosing the nature and extent of any brain damage in humans. In order to completely interpret deficits in these reflexes, their underlying anatomy and physiology must be well understood in primates. To address the questions raised above, the proposed experiments will be done in Rhesus monkeys trained to track a visual target. Anatomical and electrophysiological studies will investigate the sources of pretectal projections to the Edinger-Westphal nucleus (EW) that might mediate the PLR. The behavioral role of these pretectal projections to EW will be determined by lidocaine inactivation of specific pretectal nuclei and of the pretecto-EW fibers. Ibotenic acid injections, which should minimize potential involvement of fibers of passage, will be used to study the effects of irreversible pretectal lesions. To investigate the behavior of pretectal neurons mediating the PLR in primates, single-unit activity will be recorded from pretectal neurons identified as projecting to EW using antidromic activation and collision testing. The behavior of identified EW pupillomotor cells will also be examined using the same techniques. The relationship between their firing rate and pupillary diameter will be studied. In addition, it will be determined if the pupillomotor neurons in EW mediate both the PLR and the pupillary near response or if they mediate only the PLR.
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