DESCRIPTION (provided by applicant): Mammalian retinas are characterized by the great morphological diversity of retinal ganglion cells that send axons to a variety of central nuclei. Classification of these cells has revealed that different functional classes have distinct dendritic morphologies, cover the retina in independent mosaics, and vary in their subcortical targets. The suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL), important components of the mammalian circadian system, are targets of retinal ganglion cells. Although it is known that retinal afferents to the SCN and IGL serve to entrain the circadian system to the solar day, virtually nothing is known about the morphology of ganglion cells that project to the SCN and IGL nor about the intra-retinal entrainment circuit, critical to the functioning of our circadian system. To understand completely how light regulates our biological clock, we must understand which neurons convert light into an electrical signal and how this information is conveyed centrally to our circadian system. We hypothesize that more than a single morphological type of ganglion cell is afferent to the circadian system. Using a novel transsynaptic viral tracer developed in our laboratories, PRV-152, expressing enhanced green fluorescent protein, the hypothesis that retinal input to the SCN and IGL arises from a morphologically and neurochemically diverse population of retinal ganglion cells will be tested. Retinal ganglion cells will be examined using fluorescence light microscopy and fluorescence deconvolution and electron microscopy of identified SCN-projecting cells. In vitro whole-cell patch-clamp recording of SCN-projecting ganglion cells will be conducted to determine the responses of these cells to light stimulation. These data will provide valuable new information regarding the intraretinal entrainment circuit. Disturbances in the entrainment of our biological clock are responsible for abnormal phasing of sleep rhythms and may underlie serious affective disorders. Understanding the retinal neurons and circuits afferent to the SCN and IGL will aid in our ability to understand and treat these disturbances of phase.