Comprehensive quantification of cone dynamics

项目摘要 视觉构成了我们日常生活中的重要部分，而这个感官过程始于 一种特殊类型的感光器，称为视锥细胞，能很好地适应日光 条件、高敏锐度视力和颜色感知。锥体的基本响应性质 在分离的细胞或视网膜组织中进行的研究在很大程度上描述了光感受器。 令人惊讶的是，许多这些反应属性，如时间动力学和强度 敏感度范围，在文献中仍有争议。此外，它们中的一些与 在活体中获得的数据，以及在心理生理上测量时与人类视觉表现的数据。这个 这笔赠款的主要目的是为了更全面地描述圆锥体 视锥占优势的动物，包括灵长类动物的光感受器。这将通过联合 在完整的视网膜外植体中进行的实验与活体记录平行进行 现在可以通过自适应光学微刺激来定位单个视锥细胞。类似刺激 在每种实验方法中都将采用范例来测量强度响应 函数、到达峰值的时间的快慢、饱和刺激后的衰减动力学以及 对不断变化的背景光级别做出反应的适应速率。这些数据将用于 建立了一个完整的基于锥体光传导的响应特性理论模型 这将对视觉科学家有很大的帮助，并可能描绘出 视网膜上的活体实验和体外实验。另一个目标是详细说明一种新颖的形式是如何 通过脉冲红外双光子激发的锥体激活可用于改善空间 对锥体的刺激。双光子实验最好是与传统的1-光子交叉进行。 光子激发，以研究双光子激发机制与1-光子激发机制的不同。 光子吸收，以及确定可以产生多少内源荧光 在这样的刺激下。双光子吸收可以用来测量视锥的健康状况 循环中，了解红外刺激的基本响应特性将是 关于锥体功能和疾病的未来研究。

Project Summary Vision forms a prominent part of our daily lives, and this sensory process begins with the capture of light by a particular class of photoreceptor called cones, a class well adapted to daylight conditions, to high acuity vision, and to color perception. The basic response properties of cone photoreceptors have been largely described in studies conducted in isolated cells or retinal tissue. Surprisingly, many of these response properties, such as temporal dynamics and intensity sensitivity range, remain controversial in the literature. Moreover, some of them conflict with data acquired in vivo and with human visual performance when measured psychophysically. The primary aims of this grant are to generate a more comprehensive characterization of cone photoreceptors in cone-dominated animals, including primates. This will be achieved by conjoint experiments conducted in intact retinal explants in parallel with in vivo recordings where it is now possible to target single cones with adaptive optics microstimulation. Similar stimulation paradigms will be employed in each experimental approach to the measure intensity response functions, the rapidity of time-to-peak, the decay kinetics following saturating stimuli, and the adaptation rate in response to changing background light levels. These data will be used to develop a complete theoretical model of response properties based on cone phototransduction which will be of great use to vision scientists and may delineate the limits and boundaries of in vivo vs. in vitro experiments on the retina. An additional aim will be to detail how a novel form of cone activation—via pulsed infrared 2-photon excitation—may be used for improved spatial stimulation of cones. The 2-photon experiments are best done interleaved with traditional 1- photon stimulation in order to examine how the 2-photon excitation mechanism differs from 1- photon absorption, and also to determine how much endogenous fluorescence may be generated by such stimuli. As 2-photon absorption may be used to measure the health of the cone visual cycle, understanding the basic response properties of infrared stimulation will be foundational for future studies of cone function and disease.