Circadian Organization of the Retina

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DESCRIPTION (provided by applicant): The vertebrate retina is pervasively influenced by circadian (daily) rhythmicity. Across vertebrate species there is a wide variety of retinal rhythms including - rod and cone disc shedding; dopamine and melatonin synthesis; ERG b-wave amplitude; and visual sensitivity. The long-term goal of our research is to elucidate the retinal cell types and mechanisms critical for circadian organization of retinal function. By mapping the temporal and spatial distribution of the circadian clock gene Per 1 in the mouse retina, using transgenic mice in which neurons transcribing Per 1 are marked with a dynamic green fluorescent protein (GFP) reporter, we have established that Per 1 clock gene rhythms are concentrated in neurons of the inner retina, in part, within dopaminergic amacrine cells. In addition, the McMahon lab has recently established transgenic mouse lines which express a red fluorescent protein (RFP) reporter of tyrosine hydroxylase (TH) gene transcription to mark dopaminergic neurons. Here we propose to use these unique mouse models for functional studies examining three critical aspects of the circadian organization of the retina: I. Targeted Electophysiology of Per 1 - Expressing Dopaminergic Amacrine Cells - we will examine if these neurons exhibit intrinsic circadian rhythms in spike frequency and ionic currents. II. The Roles of Dopaminergic Amacrine Cells and Photoreceptors in Retinal Rhythmicity - we will determine if these cell populations support circadian rhythms in overall retinal clock-gene expression. III. Characterization of Per 1 - Expressing Ganglion Cells and Ganglion Cell Rhythmicity - we will determine the functional types of Per 1 - expressing ganglion cells (i.e. ON, OFF, transient), and whether ganglion cell activity is rhythmic. Completion of these aims will produce important insights into the mechanisms by which the retinal circuits match their performance to ambient conditions and provide an expanded basis for understanding the underlying mechanisms of photoreceptor degeneration and myopia, pathological eye conditions affected by the retinal circadian clock and its melatonin/dopamine outputs.