ON and OFF visual signaling in the retinal interneurons

摘要 视网膜神经元利用多种拮抗机制来塑造视觉信号处理，如ON和 OFF信号、拮抗中心环绕信号、杆状和锥状信号、瞬时和持续信号。 在这些信令机制中，ON和OFF信令被编码为形态上不同的 视网膜神经元、双极细胞、无长突细胞和神经节细胞。在视网膜内侧区域分支的视网膜神经元 内丛状层(IPL)对光刺激的开始作出反应，这种光刺激称为细胞。相比之下，关闭单元格 在IPL的外部区域分支，并对光刺激的偏移做出反应。自从被发现以来 几十年前，这一形态生理学规则似乎也没有例外 发信号。然而，最近也出现了一些例外情况。我们发现断断续续的信号 星爆无长突细胞和双极细胞中的开关。我们还发现，光适应在 开和关信号开关。在中间视光条件下，视杆和视锥都是活跃的，产生了 复杂的互动。然而，视网膜中间神经元的光诱发反应，包括双极和 无长突细胞，还没有在广泛的环境光线水平上进行系统的研究。在我们的 在拟议的研究中，我们将检验在中间条件下杆-锥相互作用转化为 视网膜双极细胞和无长突细胞光反应的开关信号。中国的长期目标是 建议的研究是检查开和关信号开关是如何在中间神经元中发生的，以及这如何在 在神经节细胞中形成棘波的作用。我们将使用全视网膜制剂进行膜片钳。 研究双极细胞和无长突细胞，以确定视觉信号对各种光刺激的反应。 特别是，我们将评估光诱发的兴奋性突触后电位(L-EPSP)在广泛的 背景光条件。我们还将检查组织在中间视野条件下的L-EPSPS 适应暗视或明视条件(目标1)。此外，我们将确定视网膜拮抗信号是如何 系统决定了开关标志的形状。我们将测试潜在的潜在机制，包括杆锥 信号相互作用，多巴胺能系统，抑制性无长突细胞的拮抗环境，以及 开-关信号通路相互作用(目标2)。然后，我们将通过执行以下命令检查切换的结果 星状突起无长突细胞的钙显象(目标3)。了解中间视觉是很重要的。 因为视杆和视锥细胞功能障碍都会导致中间视视力下降。

Abstract Retinal neurons utilize multiple antagonistic mechanisms to shape visual signal processing, such as ON and OFF signaling, antagonistic center-surround, rod- and cone-signaling, and transient and sustained signaling. Among those signaling mechanisms, ON vs. OFF signaling is coded to morphologically distinct groups of retinal neurons, bipolar, amacrine, and ganglion cells. Retinal neurons that ramify in the inner region of the inner plexiform layer (IPL) respond to the onset of a light stimulus, called ON cells. In contrast, OFF cells ramify in the outer region of the IPL and respond to the offset of a light stimulus. Since being discovered several decades ago, there appeared to be no exceptions to this morpho-physiological rule for ON and OFF signaling. However, recently, some exceptions have been revealed. We found that ON and OFF signaling switches in starburst amacrine cells and bipolar cells. We also found that light adaptation plays a crucial role in the ON and OFF sign switch. In the mesopic light condition, both rods and cones are active, generating a complicated interaction. However, light-evoked responses in retinal interneurons, including bipolar and amacrine cells, have not been systematically investigated over a wide range of ambient light levels. In our proposed studies, we will test the hypothesis that the rod-cone interaction in the mesopic condition converts the ON and OFF signs of light responses in retinal bipolar cells and amacrine cells. The long-term goal of the proposed study is to examine how the ON and OFF sign switch occurs in the interneuron and how this plays a role in shaping spikes in ganglion cells. We will use wholemount retinal preparations to conduct a patch clamp study of bipolar and amacrine cells to determine the visual signal signs in response to various light stimuli. Especially, we will assess the light-evoked excitatory postsynaptic potentials (L-EPSPs) over a wide range of background light conditions. We will also examine the L-EPSPs at the mesopic condition after the tissue is adapted to scotopic or photopic conditions (Aim 1). Also, we will determine how retinal antagonistic signaling systems shape the ON and OFF signs. We will test potential underlying mechanisms, including the rod-cone signaling interaction, the dopaminergic system, the antagonistic surround by inhibitory amacrine cells, and the ON-OFF signaling pathway interaction (Aim 2). Then, we will examine the outcome of the switch by conducting the Calcium imaging from the starburst amacrine cells (Aim 3). Understanding the mesopic vision is essential because both rod and cone dysfunction cause reduced vision in the mesopic vision.