Downstream Actions of Biophysical Mechanisms in the Visual System

视觉系统中生物物理机制的下游作用

• 批准号: 10686231
• 负责人: Michael Tri Hoang Do
• 金额: $ 59.83万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686231
• 关键词: Action Potentials; Address; Affect; Afferent Neurons; Animals; Area; Arousal; Biological; Biology; Biophysical Process; Biophysics; Brain; Cell Nucleus; Cells; Collection; Cone; Cues; Dependence; Diagnosis; Diameter; Endowment; Engineering; Goals; Individual; Iris; Knockout Mice; Knowledge; Lead; Learning; Light; Light Cell; Lighting; Measurement; Measures; Mediating; Metabolic Diseases; Methods; Miosis disorder; Molecular; Monitor; Mood Disorders; Motor; Motor output; Mus; Muscle; Mydriasis; Nervous System; Neurodegenerative Disorders; Neurologic; Newly Diagnosed; Optics; Organism; Output; Pathway interactions; Photons; Photoreceptors; Phototransduction; Presynaptic Terminals; Process; Property; Pupil; Retina; Retinal Cone; Retinal Ganglion Cells; Retinal Pigments; Rod; Sensory; Shapes; Signal Transduction; Synapses; System; Tectum Mesencephali; Testing; Time; Variant; Vertebrate Photoreceptors; Vision; Visual; Visual Acuity; Visual Pathways; Visual System; Work; awake; biophysical techniques; cell type; circadian; clinical diagnosis; experimental study; improved; in vivo; in vivo imaging; insight; light intensity; melanopsin; motor control; multiphoton imaging; operation; recruit; response; sensory mechanism; spatiotemporal; visual stimulus

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.

项目概要 该提案中的实验解决了感官信号如何触发有效行动。我们专注于光驱动 哺乳动物瞳孔的调节，其本身就值得研究，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。出现瞳孔光反应 简单但对视力至关重要；大瞳孔增加光子收集以支持昏暗光线下的视力，而 小瞳孔可减少光学像差，从而提高强光下的视力。学生调解这种权衡 跨越多个数量级的环境光强度变化，并以以下方式进行： 看起来是最佳的。我们建议研究视网膜中的分子、细胞和电路的特征如何满足 瞳孔控制的要求我们的首要假设是，这些机制经过精心调整，以适应 它们的特征通过大脑回路传播并在瞳孔中明显显现。为了测试这个 假设，我们将对小鼠应用体内方法，分析大脑第一个中继中的视网膜信号 瞳孔控制，同时监测瞳孔。我们将利用我们的视网膜知识 通过定量和系统的实验来检查他们在这些领域的行动的机制。我们将 检查具有正常视觉通路或被设计为缺乏候选机制的小鼠。而且， 我们将采用离体方法来阐明选择的机制，以便我们可以分析它们的体内影响 具有更高的精度。总而言之，这些实验将揭示瞳孔光反应的起源， 提出感觉信息如何影响运动动作的问题，并深入了解感觉信息影响运动动作的步骤 生物组织较低水平的机制影响整个动物。