Downstream Actions of Biophysical Mechanisms in the Visual System

项目总结 这项提案中的实验解决了感觉信号如何触发有效行动的问题。我们专注于光驱动 调节哺乳动物的瞳孔，这本身就值得研究，并提供了一个易于处理的系统 了解从光子捕获到电机输出的步骤。出现了瞳孔光反应。 简单，但对视力至关重要；大的瞳孔增加光子收集以支持在昏暗的光线下的视力，而 小的瞳孔可以减少光学像差，从而在强光下提高视力。学生参与了这一权衡 跨越几个数量级的环境光强度的变化，并且以一种 看起来是最理想的。我们建议研究视网膜中分子、细胞和电路的特征如何满足 对瞳孔控制的要求。我们最重要的假设是，这些机制是经过良好调整的， 他们的特征通过大脑回路传播到在瞳孔中显露出来的程度。为了测试这一点 假设，我们将把活体方法应用于小鼠，分析大脑中第一个继电器内的视网膜信号 控制瞳孔，同时监测瞳孔。我们将利用我们对视网膜的知识 利用定量和系统的实验，审查它们在这些领域的行动的机制。我们会 检查视觉通路正常或缺乏候选机制的小鼠。此外， 我们将使用体外方法来阐明选定的机制，以便我们可以分析它们在体内的影响。 精确度更高。总而言之，这些实验将揭示瞳孔光反应的起源， 告知感官信息如何影响运动动作的问题，并提供对以下步骤的洞察 较低生物组织水平的机制会影响整个动物。

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.