Downstream Actions of Biophysical Mechanisms in the Visual System

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PROJECT SUMMARY Experiments in this proposal address how sensory signals trigger effective action. We focus on light-driven modulation of the mammalian pupil, which merits study for its own sake and offers a tractable system for understanding the steps that lead from photon capture to motor output. The pupillary light response appears simple but is critical for vision; a large pupil increases photon collection to support sight in dim light, while a small pupil reduces optical aberration to sharpen visual acuity in bright light. The pupil mediates this trade-off across variations in environmental light intensity that span orders of magnitude, and does so in a manner that appears optimal. We propose to investigate how features of molecules, cells, and circuits in the retina meet the requirements of pupil control. Our overarching hypothesis is that these mechanisms are well-tuned, to the extent that their features propagate through brain circuits to manifest overtly in the pupil. To test this hypothesis, we will apply in vivo approaches to mice, analyzing retinal signals within the brain’s first relay for pupillary control while simultaneously monitoring the pupil. We will draw on our knowledge of retinal mechanisms to examine their actions in these areas, using quantitative and systematic experiments. We will examine mice that have normal visual pathways or are engineered to lack candidate mechanisms. Moreover, we will employ ex vivo methods to clarify select mechanisms, such that we can analyze their in vivo influences with greater precision. Taken together, these experiments will uncover origins of the pupillary light response, inform the question of how sensory information affects motor action, and provide insight into the steps by which mechanisms at lower levels of biological organization influence the whole animal.