SYNAPTIC TRANSMISSION AND ITS MODULATION IN THE RETINA

描述（由申请人提供）：该项目涉及NEI的基础研究优先事项，视网膜网络的适应性变化如何影响视觉处理。视网膜对变化超过十亿倍的光强度做出反应，但单个视网膜神经元只能改变其输出100倍。为了克服输入和输出之间的这种差异，视网膜神经元通过改变其响应范围以跨越环境照明强度来适应背景照明。适应发生在光感受器内，也发生在视网膜中的感受器后位置。在这个建议中，我们将研究两种形式的后受体适应。使用电生理学，药理学和解剖学方法，我们将研究视网膜回路，1）控制从视杆细胞到视锥细胞的信号转换，2）控制不同环境光水平下中心-环绕空间处理的变化。视杆细胞介导的视觉向视锥细胞介导的视觉转变的一个关键特征是抑制视杆细胞信号传导并增强视锥细胞信号传导。尽管进行了广泛的研究，但对负责这种转变的电路知之甚少。我们发现了一种新的抑制形式，当它被强光激活时，它会抑制一个关键的信号元件--视杆双极细胞的功能。在目标1中，我们确定这种新的形式的抑制在视杆双极细胞是否有助于过渡到视杆视锥视觉。环境照明水平的变化产生后感受器适应，改变中心-环绕空间处理。这种形式的空间处理对于边缘和空间对比度的检测至关重要。介导这种形式的受体后适应的电路是未知的。在目标2中，我们确定了不同环境光水平引起的中心-环绕空间处理适应性变化的电路和突触机制。

DESCRIPTION (provided by applicant): This project addresses a basic research priority of the NEI, how do adaptational changes in retinal networks affect visual processing. The retina responds to light intensities that vary over a billion-fold, but individual retinal neurons can onl vary their output 100-fold. To overcome this disparity between input and output, retinal neurons adapt to background illumination by shifting their response ranges to span ambient illumination intensities. Adaptation occurs within photoreceptors and also at post-receptor locations in the retina. In this proposal we will study two forms of post-receptor adaptation. Using electrophysiological, pharmacological and anatomical approaches, we will investigate the retinal circuits that 1) control the transition from rod to cone signaling and 2) control the variation of center-surround spatial processing at different ambient light levels. A critical feature of the transition from rod- to cone-mediated vision is to suppress rod signaling and enhance cone signaling. Despite extensive study, the circuits responsible for this transition are poorly understood. We discovered a novel form of inhibition that suppresses the function of a critical signaling element, the rod bipolar cell, when it is activated by bright light. In aim 1, we determie whether this novel form of inhibition in rod bipolar cells contributes to the transition from rod t cone vision. Changes in the level of ambient illumination produce post-receptor adaptation that alters center-surround spatial processing. This form of spatial processing is critical for the detection of edges and spatial contrast. The circuits that mediate this form of post-receptor adaptation are unknown. In aim 2, we determine the circuits and synaptic mechanisms that produce the adaptational changes in center-surround spatial processing caused by different ambient light levels.