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。我们在这个建议集中在最近发现的，但普遍形式的电路，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。当特定神经元的抑制减少而兴奋增加时，推挽相互作用就会发生，反之亦然。我们最近发现，推拉相互作用代表了双极、无突和神经节细胞的主要电路形式。在所有情况下，推拉相互作用利用互补的收敛，从ON和OFF途径的活动。当来自ON通路的兴奋增强时，来自OFF通路的抑制随之减弱，反之亦然。推挽交叉抑制在许多不同的电路中表现为：在ON和OFF双极细胞之间表现为反馈抑制，在ON和OFF视网膜神经节细胞之间表现为前馈抑制，在ON和OFF无突细胞之间表现为递归抑制。

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.