Multi-Cellular Analysis of the Retinal Network

视网膜网络的多细胞分析

• 批准号: 10343182
• 负责人: Xiaolong Jiang
• 金额: $ 40万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10343182
• 关键词: Adopted; Adoption; Affect; Behavior; Cells; Characteristics; Classification; Classification Scheme; Cone; Coupled; Coupling; Disease; Distant; Electrodes; Equation; Exhibits; Feedback; Glaucoma; Goals; Human; Individual; Injections; Kinetics; Knowledge; Lateral; Light; Light Adaptations; Light Cell; Location; Macular degeneration; Maps; Mediating; Monitor; Nervous system structure; Neurons; Night Blindness; Pathway interactions; Photoreceptors; Physiological; Property; Radial; Reaction Time; Research; Retina; Retinal Cone; Retinal Diseases; Retinitis Pigmentosa; Rod; Role; Salamander; Shapes; Signal Transduction; Stimulus; Synapses; System; Taxonomy; Techniques; Variant; Vertebrate Photoreceptors; cell type; connectome; electrical property; functional group; ganglion cell; horizontal cell; insight; light effects; network dysfunction; neural circuit; neural network; neuronal circuitry; operation; postsynaptic; presynaptic; response; retinal neuron; retinal rods; signal processing; spatiotemporal; two-dimensional; visual information; visual process; visual processing; voltage clamp; voltage gated channel

PROJECT SUMMARY/ABSTRACT Retinal circuitry is one of the most promising research platforms in the nervous system where mysteries of neural network function can be unraveled, because individual neuronal circuits therein can be selectively activated by specific natural stimuli, light. Moreover, all vertebrate retinas have similar neuronal and synaptic organizations, and thus knowledge learned from one species can be applied to others, including humans whose neural network dysfunction in disease states manifests. While significant progress has been made in understanding cell types and signal spreading within retinal circuits, we still do not have a comprehensive picture of cell type taxonomy in the retina and their wiring principles, slowing the progress toward a circuit-level mechanistic understanding of how the retina processes visual information. For example, due to the limitation of existing single- or dual- recording techniques, it is difficult to study synaptic connectivity between distinct cell types in the retinal circuit. In addition, as sensitivity and waveform of various cell types change with levels of light adaptation and duration of retinal isolation, single-electrode recordings in different retinas and/or under different adaptation conditions result in response variations and inconsistencies, confounding the functional classification of cell types in the retina. In this application, we will adopt the newly available multi-patch recording system to overcome these issues by recording simultaneous responses and synaptic connectivity of up to 8 retinal neurons. This approach will help to integrate piecemeal experimental results from previous studies into a coherent framework representing the network behavior of the vertebrate retina, which is not feasible with the existing single- or dual- electrode recording techniques. There are 4 Specific Aims. Aim 1 is to study spatiotemporal properties of electric signal spread in the coupled rod photoreceptor network and how HCN channels shape the network behavior. Aim 2 is to compare light response amplitude, waveform, and kinetics of the six types of bipolar cells (BCs) or three functional groups of ganglion cells (GCs) recorded simultaneously in the same dark-adapted retina, and the effects of light adaptation on these responses. Aim 3 is to study profiles of synaptic connectivity between rods at different retinal locations and various types of BCs, and the roles of horizontal cells (HCs) in the rod-HC- cone feedback pathway. Aim 4 is to establish a comprehensive connectivity map between various types of BCs and GCs, and contributions of individual BCs to the light responses of various types of GCs. Results obtained will provide new insights into how coupled photoreceptor networks process visual signals, how adaptation differentially alters light responses of various types of BCs and GCs, and how individual BCs mediate photoreceptor-BC-GC parallel information channels and how multiple retinal neurons function together in processing visual information. A comprehensive connectivity map for lateral synapses in the rod coupled network and radial synapses between various types of BCs and GCs may mark the beginning of establishing a “functional connectome” for the retina.

项目概要/摘要 视网膜回路是神经系统中最有前途的研究平台之一，其中神经系统的奥秘 网络功能可以被解开，因为其中的各个神经元回路可以被选择性地激活 特定的自然刺激，光。此外，所有脊椎动物的视网膜都有相似的神经元和突触组织， 因此，从一个物种学到的知识可以应用于其他物种，包括其神经网络的人类 疾病状态下表现出功能障碍。虽然在了解细胞类型方面取得了重大进展 和视网膜回路内的信号传播，我们仍然没有细胞类型分类的全面了解 视网膜及其布线原理，减缓了电路级机械理解的进展 视网膜如何处理视觉信息。例如，由于现有单或双的限制 由于记录技术的存在，很难研究视网膜回路中不同细胞类型之间的突触连接。 此外，由于各种细胞类型的灵敏度和波形随着光适应水平和持续时间的变化而变化 视网膜隔离，不同视网膜和/或不同适应条件下的单电极记录 导致反应变化和不一致，混淆了细胞类型的功能分类 视网膜。在此应用中，我们将采用新推出的多补丁记录系统来克服这些问题 通过记录多达 8 个视网膜神经元的同时反应和突触连接来解决问题。这种做法 将有助于将先前研究的零碎实验结果整合到一个连贯的框架中 代表脊椎动物视网膜的网络行为，这对于现有的单或双视网膜是不可行的 电极记录技术。有 4 个具体目标。目标1是研究电的时空特性 耦合杆光感受器网络中的信号传播以及 HCN 通道如何塑造网络行为。 目标 2 是比较六种双极细胞 (BC) 或双极细胞的光响应幅度、波形和动力学 在同一个暗适应视网膜中同时记录的神经节细胞（GC）的三个功能组，以及 光适应对这些反应的影响。目标 3 是研究突触连接的概况 视网膜不同位置的视杆细胞和各种类型的BC，以及视杆细胞中水平细胞（HC）的作用-HC- 锥体反馈通路。目标4是建立各类BC之间的全面连通性图 和 GC，以及单个 BC 对各种类型 GC 的光响应的贡献。获得的结果 将为耦合光感受器网络如何处理视觉信号、如何适应提供新的见解 不同类型 BC 和 GC 的光反应发生差异，以及个体 BC 如何介导 光感受器-BC-GC并行信息通道以及多个视网膜神经元如何在 处理视觉信息。杆耦合网络中横向突触的综合连接图 各种类型的BC和GC之间的放射状突触可能标志着建立“功能性”的开始 视网膜的连接组”。