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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

基本信息

批准号：
10501670
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
项目类别：
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/10501670
关键词：
Action Potentials Address Affect Afferent Neurons Animals Area Arousal Biological Biology Biophysical Process Biophysics Brain Caliber Cell Nucleus Cells Collection Cues Dependence Diagnosis 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 Nervous system structure Neurodegenerative Disorders Neurologic Optics Organism Output Pathway interactions Photons Photoreceptors Photosensitivity Phototransduction Presynaptic Terminals Process Property Pupil Retina Retinal Cone Retinal Ganglion Cells Retinal Pigments Seeds Sensory Shapes Signal Transduction Synapses System Testing Time Variant Vertebrate Photoreceptors Vision Visual Visual Acuity Visual Pathways Visual system structure 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 retinal rods sensory mechanism spatiotemporal visual stimulus

项目摘要

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.

项目总结