Neural coding of interneuron populations in the retina

描述(申请人提供)：像大脑的许多神经回路一样，视网膜是由具有非常不同的解剖和生理特性的细胞网络组成的。视网膜和皮质中最多样的细胞类型是抑制性中间神经元。视网膜无长突细胞由30多种细胞组成，影响作为视网膜输出细胞的神经节细胞的反应。虽然无长突细胞的解剖学和生理学研究由来已久，但对于它们是否具有特定和不同的作用，而不是每个细胞都具有相似的一般功能，人们知之甚少。理解……的重大障碍 在研究不同群体中的单个细胞时，抑制中间神经元一直是技术上的限制。这一建议试图利用一种新的方法来表征抑制性无长突细胞群体，该方法在使用电极阵列同时记录神经节细胞群体的同时光学记录无长突细胞群体的视觉反应。这个项目的重点是对运动视觉刺激的反应，这在生态上很重要，对行为和感知至关重要。这项建议的第一个目的是测量几乎完整的无长突细胞群体对运动刺激的反应，并将这些反应与神经节细胞群体中同时记录的反应进行比较。通过测量无长突细胞和神经节细胞群体之间反应的相似性，这些实验将检验无长突细胞被分为两大类的假设：一类类似于更简单的双极细胞代表，另一类与特定的视网膜神经节细胞更密切相关。该方案的第二个目的是使用光学成像和同时的细胞内和多电极记录来检验假设，即无长突细胞抑制神经节细胞，尽管无长突细胞之间首选的视觉刺激有很大的差异，但在视觉运动下，无长突细胞抑制神经节细胞。最后，这项提议的第三个目的将利用我们的新方法，直接干扰细胞内的单个中间神经元，以测试许多类型的无长突细胞是否作用于减少不同类型的神经节细胞群中的相关性 自然刺激，从而创建视觉场景的有效表示。这些研究将 不仅增加了抑制群体如何表示和转换视觉信息的知识，而且还将测试适用于所有神经回路的一般原理。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标是通过用高分辨率电子电路取代受损视网膜的功能来治疗常见疾病，如老年性黄斑变性和视网膜色素变性。对视网膜神经编码的测量和执行的计算将直接用于将其整合到这些假体系统中。

DESCRIPTION (provided by applicant): Like many neural circuits of the brain, the retina is composed of a network of cells with greatly varying anatomical and physiological properties. The most diverse types of cells, both in the retina and cortex, are inhibitory interneurons. Retina amacrine cells comprise over thirty types and influence the responses of ganglion cells, the output cells of the retina. Although the anatomy and physiology of amacrine cells have long been studied, there is little understanding as to whether they have specific and distinct roles, rather than each serving a similar, general function. A substantial barrier to the understanding of inhibitory interneurons has been technical limitations on studying single cells among a diverse population. This proposal seeks to characterize the population of inhibitory amacrine cells using a novel approach to optically record the visual responses of the amacrine cell population while simultaneously recording populations of ganglion cells using an electrode array. This project focuses on responses to moving visual stimuli, which are ecologically important and critical to behavior and perception. The first aim of this proposal will measure the responses of a nearly complete amacrine population to moving stimuli and compare these with simultaneously recorded responses in the ganglion cell population. By measuring the similarity in responses between amacrine and ganglion cell populations, these experiments will test the hypothesis that amacrine cells are divided into two broad classes: one that resembles the more simple bipolar cell representation and one that is more tightly correlated with specific retinal ganglion cells. Te second aim of this proposal uses optical imaging and simultaneous intracellular and multielectrode recording to test the hypothesis that amacrine cells inhibit ganglion cells that the are correlated with under visual motion, despite the wide variation of preferred visual stimuli across amacrine cells. Finally, the third aim of this proposal will take advantage of our novel approach of directly perturbing individual interneurons intracellularly to test whether many types of amacrine cells act to reduce correlations in the ganglion cell population for different types of natural stimuli, thus creating an efficient representation of the visual scene. These studies will not only add to the knowledge of how an inhibitory population represents and transforms visual information, but will also test general principles applicable to all neural circuits. The results wll 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 and the computations that are performed will be directly useful for incorporation into these prostheses systems.