Single photoreceptor mapping of visual neurons in vivo with adaptive optics microscopy.

我们对人类视觉感知的神经基础的理解仍然惊人地不完整，因为人类和旧世界灵长类动物在视觉解剖学和生理学方面在许多方面都是哺乳动物中独一无二的，这使得实验和遗传研究非常具有挑战性。视网膜水平的研究几乎完全是在组织外植体中进行的，目前还不清楚视网膜的正常运作程度。在皮层水平上，研究人员不得不依赖于对每个研究对象的感光细胞数量和敏感性的假设，这些假设最近变得不那么站得住脚了。一种新的多波长微刺激器配备了自适应光学（AO）校正，现在绕过这些障碍。微刺激器允许在真实的时间中对感光器马赛克成像，同时刺激活体眼睛中的单锥感光器。因此，不仅可以确定位置，还可以确定波长灵敏度（S、M和L）以及单个光感受器对神经或行为响应的贡献。在我的项目中，我将在激活单个视锥细胞的同时，从猕猴的丘脑或皮质中记录细胞外神经元，以创建第一个“视锥地图”，作为长期熟悉的中央视觉神经元感受野的基础。在细胞水平上作图的优点是（1）了解来自单个光感受器的信号如何在视觉系统的各个水平上组合或转换，（2）解决色觉生理学中的几个当前争议（例如，视锥性），以及（3）为视网膜疾病的微周边评估和相关治疗的进展提供基础

Our understanding of the neural basis of human visual perception remains startlingly incomplete, because humans and Old World primates are in many ways unique among mammals in their visual anatomy and physiology, making experimental and genetic research quite challenging. Research at the retinal level has been almost exclusively performed in tissue explants, where it is unclear how close to normal the retina is operating. At the cortical level, researchers have had to rely on assumptions about photoreceptor populations and sensitivities in each subject studied, assumptions that lately have become less tenable. A new multi-wavelength microstimulator outfitted with adaptive optics (AO) correction now circumvents these hurdles. The microstimulator allows to image the photoreceptor mosaic in real time, while simultaneously stimulating single cone photoreceptors in the living eye. Thus, not only the position but also the wavelength sensitivity (S, M and L) as well as the contribution of single photoreceptors to neural or behavioral responses can be determined. For my project, I will record extracellularly from neurons in the thalamus or cortex of macaques while activating single cones, to create the first 'cone maps' that underlie the long-familiar receptive fields of central visual neurons. The advantages of mapping at the cellular level will be (1) to learn how the signals derived from single photoreceptors are combined or transformed at various levels of the visual system, (2) to resolve several current controversies in color vision physiology (e.g. cone opponency), and (3) to provide the foundation for advances in microperimetric assessment of retinal disease and associated therapies