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非常不完整，因为人类和东半球灵长类动物在视觉解剖学和生理学上在许多方面都是哺乳动物中独一无二的，这使得实验和基因研究非常具有挑战性。视网膜水平的研究几乎都是在组织移植中进行的，目前还不清楚视网膜在多大程度上接近正常。在皮层层面，研究人员不得不依赖于对每个被研究对象的光感受器数量和灵敏度的假设，而这些假设最近变得不那么站得住脚了。一种配备自适应光学（AO）校正的新型多波长微刺激器现在绕过了这些障碍。微刺激器可以实时成像光感受器马赛克，同时刺激活体眼睛中的单锥体光感受器。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反应的贡献。在我的项目中，我将在激活单个视锥细胞的同时，从猕猴的丘脑或皮层中记录神经元的细胞外活动，以创建第一个“视锥地图”，它是长期以来熟悉的中央视觉神经元接受野的基础。在细胞水平上绘制的优势将是(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)解决当前色觉生理学中的几个争议（例如视锥对立），(3)为视网膜疾病的微周评估和相关治疗提供基础

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