Signal Processing in the Inner Retina

描述(申请人提供)：在白天条件下，视力依赖视锥感光细胞和视锥驱动的视网膜回路。视锥感受器在儿童疾病(如视网膜色素变性)和老年人疾病(如黄斑变性)期间都容易受到损害或破坏。对这些疾病引起的视锥细胞介导的视力异常的认识取决于我们对正常视网膜视锥细胞环路功能的理解。大多数常见的实验哺乳动物(如大鼠和兔子)具有视杆优势的视网膜，不太适合研究视锥细胞介导的视觉的基础回路。作为另一种选择，我们率先使用了地面松鼠视网膜，其中高达95%的光感受器是视锥细胞，并且突触后双极细胞丰富，易于获取以进行详细的电生理测量。 一道闪光在视锥感光器中产生一种“模拟”信号，这种信号根据强度分级，并在持续时间上相对持续。锥体光感受器中的信号随后在锥体到双极细胞突触的两条功能通路上被划分为：开中心和偏离中心。在已发表的工作和初步结果中，我们已经表明，根据其信号的时间特征，可以进一步细分开和关双极细胞。因此，在双极细胞上解剖上不同的~4种地松鼠中，只有一种(B5)在开灯时能发出全有或全无Na+动作电位的信号。同样，在~4种类型的Off双极细胞中，有1种(B2)具有快速的AMPA受体，并能在关闭时产生反弹的去极化。鉴于它们的瞬变光反应，我们的目标是测试b5和b2细胞是否驱动在一步光开始或偏移时产生瞬时反应的视网膜神经节细胞类别。具体地说，我们将确定a)b5和b2细胞是否在内丛状层与ON和OFF暂时性细胞共层并进行解剖接触；b)b5和b2细胞是否为暂时性神经节细胞提供一过性突触输入；以及c)以及b5和b2细胞是否引起ON和OFF暂时性神经节细胞的暂时性棘波反应。

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.