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.

项目摘要 这个提议中的实验解决了感觉信号如何触发有效的行动。我们专注于光驱动 调制的哺乳动物瞳孔，这值得研究，为自己的缘故，并提供了一个易于处理的系统， 理解从光子捕获到电机输出的步骤。瞳孔对光反应出现 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 较小瞳孔减少光学像差以在强光下使视觉敏锐度变锐利。瞳孔调节着这种权衡 跨越跨越数量级的环境光强度的变化，并且这样做的方式， 似乎是最佳的。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 学生控制的要求。我们的首要假设是，这些机制是良好的调整， 他们的特征通过大脑回路传播到瞳孔中。为了验证这一 假设，我们将在体内的方法应用于小鼠，分析视网膜信号内的大脑的第一个中继， 瞳孔控制，同时监测瞳孔。我们将利用我们对视网膜的了解 通过定量和系统的实验，审查它们在这些领域的行动。我们将 检查具有正常视觉通路或被改造为缺乏候选机制的小鼠。此外，委员会认为， 我们将采用离体方法来阐明选择的机制，这样我们就可以分析它们在体内的影响 更精确的方式总之，这些实验将揭示瞳孔光反应的起源， 告知感觉信息如何影响运动动作的问题，并提供洞察力的步骤， 生物组织较低水平的机制影响整个动物。