Optical and electrical population recording from two stages of the retinal code

描述（由申请人提供）：神经回路是大脑的处理单元，由数千或数百万个神经细胞的网络形成，这些神经细胞转换信息。视网膜是中枢神经系统（CNS）中唯一可以完整移除的神经回路，其整个自然输入以毫秒级的精度传递到数十万个细胞。它也是中枢神经系统的唯一神经回路，在疾病的情况下可能被电子假体取代。这一治疗目标的一个实质性障碍是对视网膜信息内部处理的详细理解-神经代码。 为了理解视网膜回路中两个连续的处理层，我们将采取分而治之的方法来理解神经代码，方法是使用一种新颖的技术组合在回路中的两个不同层次上同时记录。视觉场景从视频监视器投射到孤立的、完整的蝾螈或小鼠视网膜的感光层上。红外双光子激光扫描显微镜与电压敏感染料结合使用，以记录约100个中间神经元的活动。为此，我们将使用二次谐波成像，这是一种使用具有最小药理作用的染料选择性成像神经元膜电位的技术。同时，一个由60个电极组成的阵列被用来记录视网膜输出细胞中的动作电位，视网膜输出细胞包括视神经。我们将使用在视网膜的两层测量的视觉反应，分别建模外部和内部视网膜处理。我们还将使用来自中间神经元和神经节细胞群体的同步记录来测试内层视网膜是否通过减少其突触输入中包含的冗余来压缩视觉场景。这些结果将立即适用于新兴的视网膜假体领域。视网膜假体系统的目的是通过用高分辨率电子电路替代受损视网膜的功能来治疗流行疾病，例如年龄相关性黄斑变性和色素性视网膜炎。视网膜神经编码的测量将直接用于并入视网膜下和视网膜前假体系统。 公共卫生相关性：这项研究使用光学成像和多电极记录来研究脊椎动物视网膜细胞如何通过视神经处理和传递信息。视网膜是一个由许多细胞类型组成的复杂网络，每种细胞都携带着关于视觉场景的不同方面的信息。通过了解这种转化是如何发生的，我们将更好地了解这些细胞及其连接在视网膜疾病期间是如何退化的。这些信息在设计视网膜退行性疾病的治疗方法时也是必不可少的。特别是，因为这些研究将在两个不同的水平上产生视网膜神经代码的测量结果，结果将立即适合纳入电子视网膜假体系统。

DESCRIPTION (provided by applicant): Neural circuits are the processing units of the brain, formed by networks of thousands or millions of nerve cells that transform information. The retina is the only neural circuit in the central nervous system (CNS) that can be removed intact and its entire natural input delivered to hundreds of thousands of cells with millisecond precision. It is also the only neural circuit of the CNS that can potentially be replaced by an electronic prosthesis in cases of disease. A substantial barrier to this therapeutic goal is a detailed understanding of the internal processing of information in the retina - the neural code. To understand the two sequential layers of processing in the retinal circuit, we will take a divide-and- conquer approach to understanding the neural code by simultaneously recording at two different levels in the circuit using a novel combination of techniques. Visual scenes are projected from a video monitor onto the photoreceptor layer of an isolated, intact salamander or mouse retina. An infrared two-photon laser-scanning microscope is used in conjunction with a voltage-sensitive dye to record the activity of ~ 100 interneurons. To do this, we will use second harmonic generation imaging, a technique that selectively images the membrane potential of neurons using dyes with minimal pharmacological effects. Simultaneously, an array of sixty electrodes is used to record action potentials in the output cells of the retina that comprise the optic nerve. We will use measured visual responses at two layers of the retina to separately model outer and inner retinal processing. We will also use simultaneous recordings from interneuron and ganglion cell populations to test whether the inner retina compresses the visual scene by reducing redundancy contained in its synaptic input. These results will have immediate applicability to the emerging field of retinal prostheses. The objective of a retinal prosthesis system is to treat prevalent diseases such as age-related macular degeneration and retinitis pigmentosa by replacing the function of the damaged retina with a high resolution electronic circuit. Measurements of the retinal neural code will be directly useful for incorporation into subretinal and epiretinal prostheses systems. PUBLIC HEALTH RELEVANCE: The proposed research uses optical imaging and multielectrode recording to study how cells of the vertebrate retina process and transmit information through the optic nerve. The retina is a complex network of many cell types, each of which carries a different aspect of information about the visual scene. By understanding how this transformation occurs, we will gain a better understanding of how these cells and their connections degenerate during retinal disease. This information is also essential in the design of treatments for retinal degenerative diseases. In particular, because these studies will produce measurements of the neural code of the retina at two different levels, the results will immediately be suitable for incorporation into electronic retinal prosthesis systems.