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

描述（由申请人提供）：我们的长期目标是揭示控制视网膜视觉处理的基本电路设计规则。我们专注于这个建议，最近发现的，但无处不在的形式的电路，利用推挽相互作用。这种电路基序存在于从神经节细胞到LGN和视觉皮层细胞的整个视觉通路中，但从未被充分研究过。推拉相互作用发生时，抑制减少，而兴奋增加在一个给定的神经元，反之亦然。我们最近发现，推拉相互作用代表了双极细胞、无长突细胞和神经节细胞中电路的主要形式。在所有情况下，推拉相互作用都利用了ON和OFF途径的互补活动的收敛。当ON通路的兴奋增加时，OFF通路的抑制也随之减少，反之亦然。推拉交叉抑制表现在许多不同的回路中：它表现为ON和OFF双极细胞之间的反馈抑制，对ON和OFF视网膜神经节细胞的前馈抑制，以及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是一种并行处理形式的基础，其中ON和OFF视觉信号的集成补偿了信号退化并增强了信号处理功能，例如共模抑制、漂移减少以及噪声减少和非线性校正。已知类似的电路在现代电子电路设计中广泛使用。这些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中的视觉信息处理提供先例。交叉通路将使用离体视网膜和视网膜切片，使用膜片钳记录进行研究。将使用药理学激动剂和拮抗剂解剖和评价突触通路。与先前建立的细胞类型的相关性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进行形态学分析来实现。 推拉交叉通路构成了整个视觉系统中信号传输和处理的基本范式。对这些回路的透彻理解将有助于我们破译视网膜和高级视觉中心处理视觉信息的策略。这种理解将提高我们诊断视网膜和高级视觉中心视觉信号处理异常的能力，治疗视觉系统疾病，并设计用假体装置增强视力的装置。

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.