Visual input to the suprachiasmatic nucleus (SCN) serves to entrain the circadian pacemaker while input to the pretectal olivary nucleus (PON) mediates the pupillary light reflex. In rodents, a population of intrinsically photoreceptive retinal ganglion cells projects to the PON and SCN, and are important to pupillary responses and entrainment of circadian rhythms. There is now compelling evidence that similar ganglion cells exist in primate retina, project to the ON and lateral geniculate nucleus, and contribute significantly to pupillary responses. The goals of the proposed studies in primates are therefore to: 1) further characterize these intrinsically-photoreceptive ganglion cells; 2) investigate their influence on the visual physiology of PON neurons; 3) examine their hypothesized projections to the SCN; 4) determine their influence on the visual physiology of SCN neurons; and 5) determine their contribution to pupillary responses in the primate. These are important research questions, since the circadian system regulates such physiologically important behaviors as activity, body temperature, and sleep/wake cycles, and the pupillary light reflex is a clinically important diagnostic tool. These studies have important implications for our understanding of the visual, circadian, and pupillary systems in primates. If, as preliminary data indicates, pupillary responses are influenced throughout much of the photopic range by inputs from intrinsically photoreceptive ganglion cells, this has important consequences for our understanding the pupillary light reflex and for its clinical evaluation. Also, if the same retinal ganglion cells project to both SCN and PON, then it will be possible to extrapolate from information that is readily derived in the pupillary system to the circadian system, where entrainment experiments take longer. Finally, beside their roles in pupil control and circadian rhythms, these ganglion cells project to the lateral geniculate nucleus and are likely to have very broad-reaching effect on other human visual behaviors.
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