Push-pull Interactions Between ON and OFF Bipolar, Amacrine and Ganglion cells

描述(由申请者提供)：我们的长期目标是揭示管理视网膜视觉处理的基本电路设计规则。在本提案中，我们将重点放在一种最近发现的、但普遍存在的利用推拉交互的电路形式上。这个回路基序存在于从神经节细胞到LGN和视皮层细胞的整个视觉通路中，但从未得到充分的研究。在特定神经元上，当抑制减少而兴奋增加时，就会发生推拉相互作用，反之亦然。我们最近发现，在双极细胞、无长突细胞和神经节细胞中，推挽相互作用是一种主要的电路形式。在所有情况下，推拉相互作用利用来自开和关路径的互补活动的汇聚。当来自ON通路的兴奋增加时，来自OFF通路的抑制随之减少，反之亦然。推挽交叉抑制存在于许多不同的回路中：表现为On和Off双极细胞之间的反馈抑制，On和Off视网膜神经节细胞的前馈抑制，On和Off无长突细胞之间的递归抑制。 这些交叉抑制相互作用构成了一种并行处理形式，其中ON和OFF视觉信号的集成补偿了信号劣化，并增强了信号处理功能，例如共模抑制、漂移减小、降噪和非线性校正。已知在现代电子电路设计中广泛使用类似的电路。这项研究的总体目标是提取视网膜回路中的功能组织原则，这将为视网膜和高级视觉中心以及其他感觉系统处理视觉信息开创先例。交叉通路将使用分离的视网膜和视网膜切片，使用膜片钳记录进行研究。将使用药物激动剂和拮抗剂对突触通路进行解剖和评估。与先前建立的细胞类型的关联将通过使用细胞内染色和斑片记录的神经元的共聚焦显微镜的形态分析来实现。 推挽交叉通路构成了整个视觉系统信号传输和处理的基本范例。彻底了解这些回路将帮助我们破译视网膜和高等视觉中心处理视觉信息所使用的策略。这一理解将增强我们诊断视网膜和更高视觉中心的视觉信号处理异常、治疗视觉系统障碍以及设计使用假体设备增强视力的设备的能力。

DESCRIPTION (provided by applicant): Our long-term goal is to uncover the fundamental circuit design rules that govern retinal visual processing. We focus in this proposal upon a recently discovered but ubiquitous form of circuitry that utilizes push-pull interactions. This circuit motif exists throughout the visual pathway from ganglion cells to cells in the LGN and visual cortex but has never been fully investigated. Push-pull interactions occur when inhibition decreases while excitation increases at a given neuron, or vice versa. We have recently discovered that push pull interactions represent a dominant form of circuitry in bipolar, amacrine and ganglion cells. In all cases, push pull interactions utilize the convergence of complementary, activity from the ON and OFF pathways. When excitation from the ON pathway increases, there is concomitant decrease in inhibition from the OFF pathway and vice versa. Push pull crossover inhibition is manifest in many different circuitries: It is expressed as feedback inhibition between ON and OFF bipolar cells, as feedforward inhibition to ON and OFF retinal ganglion cells, and recursive inhibition between ON and OFF amacrine cells. These crossover inhibitory interactions underlie a form of parallel processing where the integration of ON and OFF visual signals compensate for signal degradation and enhance signal processing functions such as common mode rejection, drift reduction, and noise reduction and non-linearity corrections. Similar circuitry is known to be used extensively in modern electronic circuit design. The overall goal of the studies is to extract principles of functional organization in the circuitry of the retina that will set precedents for processing of visual information in the retina and at higher visual centers as well as in other sensory systems. Crossover pathways will be studied using isolated retina and retinal slices, using patch clamp recording. Synaptic pathways will be dissected and evaluated using pharmacological agonists and antagonists. Correlation with previously established cell types will be implemented through morphological analysis using confocal microscopy of intracellularly-stained and patch-recorded neurons. The push-pull, crossover pathways constitute a fundamental paradigm for signal transmission and processing throughout the visual system. A thorough understanding of these circuitries will help us decipher the strategies used by the retina and higher visual centers to process the visual message. This understanding will enhance our ability to diagnose visual signal processing anomalies in the retina and higher visual centers, to treat disorders of the visual system, and to design devises for enhancing vision with prosthetic devices.