Neural mechanisms that detect defocus in the retina

检测视网膜散焦的神经机制

• 批准号: 10700107
• 负责人: William Rowland Taylor
• 金额: $ 20.06万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10700107
• 关键词: Acute; Amacrine Cells; Animals; Area; Calcium; Cells; Characteristics; Cone; Cues; Development; Electrophysiology (science); Elements; Eye; Frequencies; Functional Imaging; Functional disorder; Future; Goals; Growth; Hour; Image; In Situ; Lead; Length; Light; Maps; Measures; Methods; Monitor; Morphology; Myopia; Neurobiology; Neurons; Optics; Pathway interactions; Pattern; Photic Stimulation; Preparation; Prevalence; Process; Property; Research; Retina; Role; Sensory; Signal Transduction; Stains; Stimulus; Synapses; Testing; Vision; Visual; Visual Accommodation; Visual System; Whole-Cell Recordings; Work; candidate identification; design; detection platform; detector; emmetropization; extracellular; ganglion cell; insight; interest; lens; movie; multi-photon; neural; neuromechanism; neuronal cell body; neurotransmission; receptive field; response; retinal imaging; retinal neuron; two-photon; visual stimulus; voltage clamp

PROJECT SUMMARY A sharp retinal image is essential for accurately encoding the visual world. The focal length of the eyes' optics can be adjusted within a fraction of a second to bring object of interest into sharp focus, a process called “accommodation”. On longer timescales, hours to months, a sharp retinal image is made possible when the axial length of the eye grows to match the refractive power of the optics, a process called “emmetropization”. In order to respond appropriately, accommodation and emmetropization require the retina to detect the sign and magnitude of image defocus. It is well established that the major optical cue that signals the sign of defocus is longitudinal chromatic aberration (LCA). LCA is due to the stronger refraction of short than long wavelength light. The identity of the neurons in the retina that detect LCA signals, and how they relay the signals to the down-stream mechanisms that control eye growth and accommodation, remains one of the great outstanding puzzles in sensory neurobiology. This proposal aims to identify the retinal neurons that respond to LCA. We will use multi-photon calcium imaging to simultaneously measure responses from tens to hundreds of neurons within an area of retina under photopic adaptation levels. Patterned, chromatic images will be used to identify candidate defocus neurons. The somas of the neurons will then be targeted for single-cell whole-cell recordings to measure in detail the receptive field properties and to recover the morphology. We will also measure responses to natural scenes rendered with and without LCA calculated for the optics of the eye. Identification LCA-sensitive neurons will lay the groundwork for future studies aimed at determining how these retinal neurons ultimately control accommodation and emmetropization. These insights may also provide clues as to the origin of the mysterious, continuing increase in the prevalence of myopia and perhaps lead to development of mitigative strategies.

项目概要 清晰的视网膜图像对于准确编码视觉世界至关重要。焦点 眼睛的光学长度可以在几分之一秒内调整，以带来物体 将兴趣转变为清晰的焦点，这个过程称为“适应”。在更长的时间尺度上，小时 几个月后，当眼轴长度增长时，就可以形成清晰的视网膜图像 为了匹配光学器件的折光力，这一过程称为“正视化”。为了 为了做出适当的反应，调节和正视化需要视网膜 检测图像散焦的符号和幅度。众所周知，主要 发出散焦信号的光学线索是纵向色差 (LCA)。 LCA 是由于短波长光的折射比长波长光更强。身份 视网膜中检测 LCA 信号的神经元，以及它们如何将信号传递给 控制眼睛生长和调节的下游机制仍然是其中之一 感觉神经生物学中伟大而悬而未决的难题。该提案旨在确定 对 LCA 做出反应的视网膜神经元。我们将使用多光子钙成像 同时测量一个区域内数十到数百个神经元的反应 视网膜处于明视适应水平。带图案的彩色图像将用于 识别候选散焦神经元。然后神经元的体细胞将被靶向 单细胞全细胞记录，以详细测量感受野特性并 恢复形态。我们还将测量对使用以下命令渲染的自然场景的响应 并且没有针对眼睛光学进行 LCA 计算。识别 LCA 敏感神经元 将为未来的研究奠定基础，旨在确定这些视网膜如何 神经元最终控制调节和正视化。这些见解可能 也提供了关于神秘的起源的线索，流行率持续增加 近视的发生，并可能导致缓解策略的制定。