How vesicles send information to retinal ganglion cells

囊泡如何向视网膜神经节细胞发送信息

• 批准号: 8987567
• 负责人: MICHAEL A FREED
• 金额: $ 36万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8987567
• 关键词: 3-Dimensional; Alpha Cell; Amacrine Cells; Beryllium; Blindness; Cells; Chemical Synapse; Computer Simulation; Cone; Detection; Devices; Discrimination; Educational process of instructing; Electron Microscopy; Elements; Event; Feeds; Fluorescent Dyes; Gap Junctions; Goals; Gold; Health; Kinesin; Kinetics; Knowledge; Life; Modeling; Monitor; Neural Retina; Neurons; Noise; Ocular Prosthesis; Peroxidases; Photons; Physiologic pulse; Presynaptic Terminals; Process; Prosthesis; Proteins; Research; Resolution; Retina; Retinal; Retinal Ganglion Cells; Role; Running; Sensory; Shapes; Site; Staining method; Stains; Stimulus; Structure; Synapses; Synaptic Vesicles; System; Testing; Time; Vesicle; Vision; Visual impairment; design; ganglion cell; improved; interest; miniaturize; neural circuit; neural prosthesis; postsynaptic; postsynaptic neurons; presynaptic; presynaptic neurons; quantum; regenerative; relating to nervous system; retinal rods; ribbon synapse; vesicular release; visual information; visual stimulus; voltage

DESCRIPTION (provided by applicant): The overall goal of this research is to vertically integrate detailed knowledge about synapses and other neural elements into an overall understanding of what neural circuits do and how they are designed to do it. An important constraint on the design of a sensory circuit is noise generated by the physical stimulus and by elements of the circuit. This is epitomized by the rod synapse in the retina, whose design removes transduction noise generated within the rod. Another good example from retina is gap junctions that open and close according to the competing demands of limiting photon noise and improving spatial resolution. Also in the retina, multiple synapses converge on a single ganglion cell to average out synaptic noise. The present focus of this research is the synapse that the retinal bipolar cell makes on ganglion and amacrine cells. This synapse has an intriguing dyadic structure that brings two neurons postsynaptic to the same vesicle fusion site. Yet the purpose of this structure is not yet clear. At the mechanistic level, because vesicle fusions are random, they induce noise in the postsynaptic neuron. If the dyadic structure includes two postsynaptic ganglion cells, the synapse should induce noise correlations between them. If the postsynaptic neurons are a ganglion cell and an inhibitory amacrine cell that feeds forward to the ganglion cell, the synapse should induce correlations between excitatory and inhibitory currents within the ganglion cell. At the systems level, noise correlations between and within ganglion cells optimize the detection and discrimination of visual stimuli. To vertically integration these different levels requires experimental evidence that the two postsynaptic processes sense the same vesicle fusion event, and that the dyadic synapse induces noise correlations. Therefore the proposed research will investigate the mechanisms and structure of the dyadic synapse. To vertically integrate different levels of knowledge, it will include this mechanistic and structural information in biophysically accurate models of the retina circuit. The models will help test ideas about how dyadic synapses and other circuit elements generate noise correlations that optimize the encoding of visual information. Prosthetic visual devices need far more space and energy than the retina they are designed to supplement or replace. As we attempt to miniaturize and optimize prosthetic neural devices, the retina has much to teach us. As prosthetic devices approach the compactness of the neural retina, they will encounter the same problem that the retina does for the same reason: using a small number of stochastic elements to encode information invariably produces noise. No prosthetic device has equaled the retina's sensitivity or resolution; therefore, by understanding how the retina is designed to optimize vision in the face of noise, better prosthetic devices can be designed.

描述（由申请人提供）：这项研究的总体目标是将有关突触和其他神经元素的详细知识垂直整合到对神经回路所做的事情以及如何设计其设计的总体上。对感觉电路设计的重要限制是由物理刺激和电路元素产生的噪声。这是视网膜中的杆突触体现的，视网膜的设计消除了杆中产生的转导噪声。视网膜的另一个很好的例子是，根据限制光子噪声和改善空间分辨率的竞争要求开放和关闭的间隙连接。同样在视网膜中，多个突触会在单个神经节细胞上收敛以平均突触噪声。 这项研究的当前重点是视网膜双极细胞在神经节和无肿瘤细胞上产生的突触。该突触具有有趣的二元结构，将两个神经元的神经元带到同一囊泡融合位点。然而，这种结构的目的尚不清楚。在机械水平上，由于囊泡融合是随机的，因此它们会在突触后神经元中诱导噪声。如果二元结构包括两个突触后神经节细胞，则突触应引起它们之间的噪声相关性。如果突触后神经元是神经节细胞，并且是向神经节细胞前进的抑制性无长血管细胞，则突触应诱导神经节细胞内兴奋性和抑制性电流之间的相关性。在系统级别，神经节细胞之间和内部的噪声相关性优化了视觉刺激的检测和区分。为了垂直整合这些不同的水平，需要实验证据表明两个突触后过程感觉到相同的囊泡融合事件，并且二元突触会诱导噪声相关性。 因此，拟议的研究将研究二元突触的机理和结构。为了垂直整合不同级别的知识，它将包括这种机械和结构 视网膜电路的生物物理精确模型中的信息。这些模型将有助于测试想法 关于二元突触和其他电路元件如何产生噪声相关性，以优化视觉信息的编码。 假肢视觉设备比其设计用于补充或更换的视网膜所需的空间和能量要多得多。当我们试图微型化和优化假肢神经设备时，视网膜可以教我们很多。当假体设备接近神经视网膜的紧凑性时，它们将遇到与视网膜相同的问题，其原因是相同的原因：使用少量随机元素来编码信息总是会产生噪声。没有假体装置等于视网膜的灵敏度或分辨率；因此，通过了解视网膜的设计如何在面对噪音时优化视觉，可以设计更好的假肢设备。

项目成果

The ON pathway rectifies the OFF pathway of the mammalian retina.

• DOI: 10.1523/jneurosci.4733-09.2010
• 发表时间: 2010-04-21
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Liang Z;Freed MA
• 通讯作者: Freed MA

Retinal ganglion cells--spatial organization of the receptive field reduces temporal redundancy.

视网膜神经节细胞——感受野的空间组织减少了时间冗余。

• DOI: 10.1111/j.1460-9568.2008.06394.x
• 发表时间: 2008
• 期刊: The European journal of neuroscience
• 作者: Tokutake,Yoichiro;Freed,MichaelA
• 通讯作者: Freed,MichaelA