Signal Processing in the Inner Retina

描述（由申请人提供）：在日光条件下，视觉依赖于锥体光感受器和锥体驱动的视网膜电路。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，锥状光感受器容易受到损伤或破坏。对这些疾病引起的锥体介导视觉异常的认识取决于我们对正常视网膜中锥体回路功能的理解。大多数常见的实验室哺乳动物（例如，大鼠和兔子）具有杆状视网膜，不太适合研究锥体介导视觉的电路。作为替代方案，我们率先使用了地鼠视网膜，其中高达95%的光感受器是视锥细胞，其中突触后双极细胞丰富，易于进行详细的电生理测量。

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.