Mechanisms of Synaptic Processing in the Retina

描述（由申请人提供）：视网膜的输出包括10-15种不同类型的视网膜神经节细胞的活动，每种细胞都针对特定的空间和时间特性进行了优化。通过去除冗余信息的机制，优化了视网膜神经元在有限带宽上的信息传输。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，提高信噪比和信息的传输。我们假设预测编码也可以通过减去更复杂的统计数据（如对比度、颜色、运动或方向）来实现。环绕拮抗作用首先在外层视网膜通过水平细胞反馈到光感受器而产生，然后传播到双极细胞，因此必然是所有神经节细胞和无突细胞所固有的，但在那里它与内部视网膜产生的环绕作用混合在一起。从无突细胞反馈到双极细胞终端，从无突细胞前馈到神经节细胞的树突，使其周围具有非线性特性。视网膜内外环都是视觉功能的基础，但它们的相对作用尚不清楚。我们提议检验一些关于腺突起和神经节细胞周围的假设。我们将记录活的无突细胞和神经节细胞，测量其内部和外部视网膜包围的时空范围，并使用神经递质GABA和甘氨酸阻滞剂区分线性和非线性包围特性。我们将测试反馈到双极细胞终末的假设，产生超过一种突触后神经节细胞类型共同的周围抑制。其次，我们将确定哪些特定神经节细胞类型特有的复杂感受野特性是由前馈抑制介导的。第三，我们将研究特定的无毛细胞类型的感受野特性，以确定它们是否可以传递在神经节细胞中观察到的非线性特性。实验将集中于2种具有良好特征的同心圆神经节细胞，即快变（BT）和快变持续（BS）细胞，以及2种具有良好特征的复杂神经节细胞，即开-关定向选择细胞（DSGC）和局部边缘检测器（LED），以及几种窄视场和宽视场无突细胞。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许多类型的眼病中出现的问题，并有助于生物工程师开发更接近活体视网膜功能的假视网膜设备。公共卫生相关性：失明影响着数百万美国人，对公共和私营卫生部门造成了重大损失。开发能够替代视网膜功能的假体装置是目前正在积极寻求的治疗途径。该项目将阐明正常视网膜中神经信号的特性，这将允许开发能够更好地模拟正常视网膜功能的假体设备。

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.