Comprehensive quantification of cone dynamics

视网膜中的视锥感光细胞调节绝大多数日常视觉知觉 它们的反应代表了由下游神经元处理的初始视觉信号。作为一名 结果，表征人类视锥细胞感光细胞的反应特性是解决差距的关键 在我们的视网膜生理学知识，并最终，人类视觉的神经基础。大多数关于 哺乳动物的视锥细胞电生理学已经在体外进行。尽管这允许广泛的 对照，有证据表明，在体内和体外制剂下，锥体行为存在差异。至 为了在体内解决这个问题，我们的实验室开发了一种技术，在这种技术中，锥体响应特性可以 利用自适应光学扫描激光进行单视锥靶向视网膜刺激的体内研究 眼底镜(AOSLO)结合下游神经元的生理记录。 除了使用普通的单光子刺激外，我们还将使用双光子刺激来检查 利用AOSLO系统对锥形感光色素的直接双光子刺激的性质。尽管在那里 存在直接双光子刺激视锥的证据(Palczewska等人)。2014)，在那里 仍然有可能这种感觉是由内源性视网膜的次级荧光引起的 荧光团。通过交叉单光子和双光子刺激锥体，我们也将能够量化 这两种刺激在光捕捉方面的差异。在此项目过程中收集的数据 也将被用来研究视束和外侧膝状体(Lgn)的神经编码。 因为它与心理物理亮度阈值有关。因为LGN神经元接收到更多的尖峰 在它们产生之前，LGN必须选择性地转播某些尖峰(Sincich等人)。2007年，Rathbun等人。 2010)。在给定刺激检测概率下的LGN峰模式如何导致知觉 阈值不是很清楚，尤其是对单锥体刺激的反应。 这项提议的目的是描述猕猴视锥感光细胞的反应特性。 并确定视网膜神经节细胞或LGN中的棘波编码是否为人类设定了界限 心理物理亮度阈值性能。在目标1中，我们将使用视锥目标刺激来 测量锥体强度响应函数、恢复到闪光的时间进程和适应 重复的刺激。通过加入双光子刺激，我们将量化间接激发的程度 当附近的内源荧光团在双光子激发后发出光时，圆锥体。在目标2中， 对目标1中记录的棘波序列的分析将用于确定神经测量反应如何 功能涉及心理物理反应功能。这项研究的发现将解决 我们对早期视觉系统中神经活动的理解存在根本差距 双光子感知的潜在机制。

Cone photoreceptors in the retina mediate the vast majority of day-to-day visual percepts in humans, and their responses represent the initial visual signals processed by downstream neurons. As a result, characterizing the response properties of human cone photoreceptors is key to addressing gaps in our knowledge of retinal physiology, and ultimately, the neural basis of human vison. Most studies of mammalian cone electrophysiology have been conducted in vitro. Although this allows extensive control, evidence suggests differences exist in cone behavior under in vivo and in vitro preparations. To approach this issue in vivo, our lab developed a technique in which cone response properties can be elucidated in vivo using single-cone targeted retinal stimulation with an adaptive optics scanning laser ophthalmoscope (AOSLO) in conjunction with physiological recordings from downstream neurons. In addition to using normal single photon stimuli, we will utilize 2-photon stimuli to examine the nature of direct 2-photon stimulation of cone photopigment using the AOSLO system. Though there exists evidence suggesting direct 2-photon stimulation of cones occurs (Palczewska et al. 2014), there remains the possibility that such percepts arise from secondary fluorescence of endogenous retinal fluorophores. By interleaving single and 2-photon stimulation of cones, we will also be able to quantify the differences in light capture between the two stimuli. Data gathered over the course of this project will also be used to examine neural encoding in the optic tract and the lateral geniculate nucleus (LGN) as it relates to psychophysical luminance threshold. Because LGN neurons receive many more spikes than they produce, the LGN must selectively relays certain spikes (Sincich et al. 2007, Rathbun et al. 2010). How the LGN spike patterning at a given stimulus detection probability leads to perceptual threshold is not understood, particularly in response to single cone stimulation. The goal of this proposal is to characterize the response properties of macaque cone photoreceptors in vivo and determine if spike coding in retinal ganglion cells or the LGN set the bounds for human psychophysical luminance threshold performance. In Aim 1, we will use cone-targeted stimuli to measure cone intensity response functions, time course of recovery to a flash, and adaptation to repeated stimuli. By incorporating 2-photon stimuli, we will quantify the extent of indirect excitation of cones when nearby endogenous fluorophores emit light following 2-photon excitation. In Aim 2, analysis of the spike trains recorded in Aim 1 will be used to determine how the neurometric response function relates to psychophysical response functions. The findings of this study will address fundamental gaps in our understanding of neural activity in the early visual system and the mechanisms underlying 2-photon perception.