Biophysical limitations to signal transmission in the mammalian retina

描述（由申请人提供）：对于捕食者和被捕食者来说，夜间视力具有相当大的进化优势，许多哺乳动物，包括人类，都具有出色的夜视能力。人类能够感知产生单光子吸收的微弱闪光的概率约为百分之一，这表明单光子产生的信号通过视网膜可靠地传递到大脑。我们对视杆光感受器如何将单个光子编码为电信号有了详细的了解，但对这些微小信号如何通过视网膜传输知之甚少。本研究的总体目标是获得通过视网膜的单光子突触传输的定量理解。我们将使用小鼠作为模型系统，因为它们具有发达的夜视能力，并为哺乳动物的视杆视觉制作一个优秀的模型系统。单光子信号的记录将来自连接杆状细胞和神经节细胞的神经元链中的每个神经元。对暗光闪烁产生的电压和电流信号进行分析。具体目标包括：1)确定杆状突触增益控制机制；2)确定杆状突起细胞中控制收敛噪声的非线性性质；3)解析神经节细胞中的单光子信号。我们对正常视网膜功能的理解的进步将提高我们对视网膜疾病导致的功能障碍的理解。我们的研究结果将与引起夜盲症的疾病特别相关。

DESCRIPTION (provided by applicant): Seeing at night has considerable evolutionary advantages both for predators and prey, and many mammals, including humans, have excellent night vision. Humans can perceive dim light flashes that produce single photon absorption in about 1 in 100 rods, which indicates that signals generated by single photons are reliably transmitted through the retina to the brain. We have a detailed understanding about how the rod photoreceptors encode single photons as electrical signals, but relatively little is known about how these tiny signals are transmitted through the retina. The general goal of this research is to gain a quantitative understanding of single photon synaptic transmission through the retina. We will use the mouse as a model system, because they have a well-developed night vision, and make an excellent model system for mammalian rod vision. Recordings of single photon signals will be made from each neuron in the chain of neurons connecting the rods to the ganglion cells. Voltage and current signals generated in response to dim light flashes will be analyzed. Specific aims include 1) determining the mechanisms of gain control at the rod synapse, 2) determining the nature of the non-linearity that controls convergent noise in the rod All amacrine cells, 3) resolving the single photon signal in ganglion cells. Advances in our understanding of normal retinal function will improve our understanding of the dysfunctions that result from retinal disease. Our results will have particular relevance to diseases that cause night blindness.