Mechanisms of Synaptic Processing in the Retina

视网膜突触处理机制

• 批准号: 7623043
• 负责人: William Rowland Taylor
• 金额: $ 38.07万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623043
• 关键词: Affect; Amacrine Cells; American; Back; Biomedical Engineering; Blindness; Brain; Buffers; Cells; Characteristics; Clinical; Code; Cods; Color; Complex; Dendrites; Dependence; Development; Devices; Environment; Exhibits; Eye; Eye diseases; Feedback; Ganglia; Glycine; Health; Inner Plexiform Layer; Lateral; Life; Location; Measures; Mediating; Morphology; Motion; Myxoid cyst; Neurons; Neurotransmitters; Noise; Output; Pattern; Peripheral; Photoreceptors; Process; Property; Prosthesis; Relative (related person); Research Personnel; Retina; Retinal; Retinal Ganglion Cells; Role; Signal Transduction; Structure; Synapses; Testing; Vision; Visual; Visual system structure; Work; cell type; cost; detector; feeding; gamma-Aminobutyric Acid; ganglion cell; horizontal cell; information processing; luminance; object motion; outer plexiform layer; postsynaptic; public health relevance; receptive field; receptor; relating to nervous system; research study; response; retinal neuron; statistics; transmission process

DESCRIPTION (provided by applicant): The output from the retina comprises the activity of 10-15 distinct classes of retinal ganglion cells, each optimized for specific spatial and temporal properties. Information transfer over the limited bandwidth available to retinal neurons is optimized by mechanisms that remove redundant information. One hypothesis for such a mechanism is predictive coding, which collects luminance signals from the surrounding regions and subtracts them from the center response, thereby removing correlations, and enhancing the signal-to-noise ratio and transmission of information. We hypothesize that predictive coding can also be implemented by the subtraction of more complex statistics such as contrast, color, motion, or orientation. Surround antagonism, generated first in the outer retina by horizontal cell feed-back onto photoreceptors, propagates to bipolar cells and therefore must be inherent in all ganglion and amacrine cells, but there it is mixed with a surround generated from the inner retina. Feedback from amacrine cells onto bipolar cell terminals and feed-forward from amacrine cells onto a ganglion cell's dendrites endow its surround with non-linear properties. Both outer and inner retinal surrounds are fundamental for the function of vision, but their relative roles are unknown. We pro- pose to test several hypotheses about amacrine and ganglion cell surrounds. We will record from live amacrine and ganglion cells, measure the spatio-temporal extent of their inner and outer retinal surrounds, and using blockers of neurotransmitters GABA and glycine, distinguish between the linear and nonlinear surround properties. We will test the hypothesis that feedback onto a bipolar cell's terminals produces surround inhibition common to more than one postsynaptic ganglion cell type. Second, we will determine which complex receptive field properties unique to a specific ganglion cell type are mediated by feed-forward inhibition. Third, we will study receptive field properties of specific amacrine cell types to determine whether they can convey the nonlinear properties observed in ganglion cells. The experiments will focus on 2 well-characterized concentric ganglion cells, the brisk-transient (BT) and brisk-sustained (BS) cells, and on 2 well characterized complex ganglion cells, the On-Off direction-selective cells (DSGC), and local-edge-detectors (LED), as well as several types of narrow- and wide-field amacrine cell. This work will collect information about retinal structure and function vital to a better understanding of information processing in the visual system and the brain. It will help to understand better how the eye functions, which will help clinical researchers determine what has gone wrong in many types of eye disease and bioengineers in developing prosthetic retinal devices that more closely match the function of the living retina. PUBLIC HEALTH RELEVANCE: Blindness affects millions of Americans and constitutes a significant cost to public and private health sectors. Development of prosthetic devices that can replace the function of the retina is an avenue of treatment that is being actively pursued. This project will elucidate the properties of neural signals in normal retina, which will allow development of prosthetic devices that can better mimic normal retinal function.

描述(由申请人提供)：视网膜的输出包括10-15个不同类别的视网膜神经节细胞的活动，每个细胞都针对特定的空间和时间属性进行了优化。在视网膜神经元可用的有限带宽上的信息传输通过删除冗余信息的机制进行优化。这种机制的一个假设是预测编码，它从周围区域收集亮度信号，并从中心响应中减去它们，从而消除相关性，并增强信噪比和信息传输。我们假设预测编码也可以通过减去更复杂的统计信息来实现，例如对比度、颜色、运动或方向。环绕拮抗首先在视网膜外部产生，由水平细胞反馈到光感受器，传播到双极细胞，因此必须是所有神经节和无长突细胞所固有的，但在那里它与从视网膜内部产生的周围混合在一起。从无长突细胞到双极细胞终末的反馈和从无长突细胞到神经节细胞树突的前馈赋予神经节细胞周围的非线性特性。视网膜外部和内部环境对视觉功能都是基本的，但它们的相关作用尚不清楚。我们建议检验关于无长突细胞和神经节细胞周围的几个假说。我们将记录活的无长突细胞和神经节细胞，测量它们视网膜内外环境的时空范围，并使用神经递质GABA和甘氨酸的阻滞剂，区分线性和非线性环境属性。我们将检验这样一个假设，即对双极细胞末端的反馈会产生不止一种突触后神经节细胞共同的周围抑制。其次，我们将确定特定神经节细胞类型特有的哪些复杂感受野特性是由前馈抑制介导的。第三，我们将研究特定类型的无长突细胞的感受场特性，以确定它们是否能够传递在神经节细胞中观察到的非线性特性。实验将集中在两个特征良好的同心神经节细胞，即快瞬变(BT)和快持续(BS)细胞，以及两个特征良好的复杂神经节细胞，开关方向选择细胞(DSGC)，局部边缘检测器(LED)，以及几种类型的窄视野和宽视野无长突细胞。这项工作将收集有关视网膜结构和功能的信息，这对于更好地理解视觉系统和大脑中的信息处理至关重要。这将有助于更好地了解眼睛的功能，这将有助于临床研究人员确定多种眼病的问题所在，并帮助生物工程师开发与活体视网膜功能更接近的假体视网膜设备。与公共卫生相关：失明影响数百万美国人，并构成公共和私营卫生部门的巨大成本。开发能够取代视网膜功能的假体设备是一种正在积极寻求的治疗方法。该项目将阐明正常视网膜中神经信号的特性，这将使开发能够更好地模拟正常视网膜功能的假体设备成为可能。