Signal Processing in the Inner Retina

描述（由申请人提供）：在日光条件下，视力取决于视锥光感受器和视锥驱动的视网膜回路。锥状光感受器在儿童期疾病（例如，色素性视网膜炎）和老年人（例如，黄斑变性）。对这些疾病引起的视锥细胞介导的视觉异常的认识取决于我们对正常视网膜中视锥细胞回路功能的理解。最常见的实验室哺乳动物（例如，大鼠和兔）具有视杆细胞主导的视网膜，并且不太适合于研究视锥细胞介导的视觉下的电路。作为替代方案，我们率先使用了地松鼠视网膜，其中高达95%的光感受器是锥细胞，并且其中突触后双极细胞丰富，易于获得详细的电生理测量。 闪光在视锥光感受器中产生“模拟”信号，其强度分级并且持续时间相对较长。视锥细胞中的信号然后在视锥细胞到双极细胞突触处被分成两个功能通路：中心上和偏离中心。我们已经表明，无论是在已发表的工作和初步结果，开和关双极细胞每个可以进一步细分，根据其信号的时间特性。因此，在4种解剖学上不同类型的地松鼠双极细胞中，只有一种（b5）可以在光照下发出全或无Na+动作电位的信号。类似地，约4种关闭双极细胞中的1种（b2）具有快速AMPA受体，并且可以在熄灯时产生反弹去极化。鉴于它们的瞬态光反应，我们的目标是测试b5和b2细胞是否驱动视网膜神经节细胞，这些细胞在光的开始或偏移时产生瞬态反应。具体而言，我们将确定a）b5和b2细胞是否与内网状层中的开和关瞬时细胞共层并进行解剖学接触; B）b5和b2细胞是否向瞬时神经节细胞提供瞬时突触输入;以及c）以及b5和b2细胞是否引起开和关瞬时神经节细胞中的瞬时尖峰响应。

DESCRIPTION (provided by applicant): Under daylight conditions, vision depends on cone photoreceptors and the cone-driven retinal circuitry. Cone photoreceptors are susceptible to damage or destruction during diseases of both childhood (e.g., retinitis pigmentosa) and in the elderly (e.g., macular degeneration). An appreciation of the abnormalities in cone-mediated vision caused by these diseases depends upon our understanding of the function of cone circuits in the normal retina. Most common laboratory mammals (e.g., rat and rabbit) have rod-dominant retinas and are less-suitable for investigations of the circuitry underlying cone-mediated vision. As an alternative, we have pioneered the use of the ground squirrel retina, in which up to 95% of the photoreceptors are cones, and in which the postsynaptic bipolar cells are plentiful and easy to access for detailed electrophysiological measurements. A flash of light generates an "analog" signal in cone photoreceptors that is graded with intensity and relatively sustained in duration. The signals in cone photoreceptors are then divided into two functional pathways at the cone to bipolar cell synapse: On-center and Off-center. We have shown, both in published work and in the Preliminary Results, that On and Off bipolar cells each can be further subdivided according to the temporal characteristics of their signals. Thus, of the ~4 anatomically distinct types of ground squirrel On bipolar cells, only one (the b5) can signal at light-on with an all-or-nothing Na+ action potential. Similarly, 1 of the ~4 types of Off bipolar cells (the b2) has fast AMPA receptors and can produce a rebound depolarization at light-off. Given their transient light responses, our goal is to test whether the b5 and b2 cells drive classes of retinal ganglion cells that produce transient responses at either the onset or offset of a step of light. Specifically, we will determine a) whether b5 and b2 cells costratify and make anatomical contacts with On and Off transient cells in the inner plexiform layer; b) whether b5 and b2 cells provide a transient synaptic input to the transient ganglion cells; and, c) and whether b5 and b2 cells cause the transient spike responses in On and Off transient ganglion cells.