Dendritic integration at the retinogeniculate synapse

视网膜原突触处的树突整合

• 批准号: 10596474
• 负责人: Hector Acaron
• 金额: $ 6.95万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-05-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596474
• 关键词: Algorithms; Axon; Behavior; Biological Models; Brain; Calcium; Dendrites; Dendrodendritic Synapse; Dorsal; Electron Microscopy; Electrophysiology (science); Ensure; Equilibrium; Exhibits; Eye; Functional Imaging; Genetic; Goals; Guidelines; Histology; Image; Individual; Interneurons; Knowledge; Label; Lateral Geniculate Body; Learning; Mediating; Methods; Mus; Nervous System; Neurodevelopmental Disorder; Neurons; Oranges; Output; Perception; Physiological; Physiology; Presynaptic Terminals; Property; Research; Resolution; Retina; Retinal Ganglion Cells; Role; Shapes; Signal Transduction; Site; Slice; Stream; Structure; Synapses; Testing; Thalamic structure; Training; Transgenic Organisms; Vertebral column; Visual; Visual System; Visual evoked cortical potential; Visualization; appendage; autism spectrum disorder; career; cell type; experimental analysis; experimental study; in vivo; in vivo calcium imaging; insight; large scale data; neural; neurotransmission; optogenetics; orientation selectivity; patch clamp; postsynaptic; presynaptic; response; retinal neuron; retinogeniculate; segregation; sensory integration; spatiotemporal; superresolution microscopy; synaptic function; visual information; visual processing

Project Summary One of the most remarkable properties of the brain is its ability to compute and integrate information. In the visual system, processing of visual scenes begins in the eye, where the underlying retinal circuitry segregates information into 30 – 40 distinct functional channels, each encoding one particular visual feature. Retinal ganglion cells (RGCs), the output neurons of the retina, relay these signals to downstream visual centers where they are integrated to mediate perception and drive behavior. The retinogeniculate synapse in the dorsal lateral geniculate nucleus (dLGN) represents the first connection between the eye and the brain and has been widely studied across multiple species. A prominent feature of the retinogeniculate synapse is that retinal inputs have a high propensity to organize into synaptic triads with inhibitory terminals and the postsynaptic dendrite creating a local circuit for fast feedforward inhibition. Recent studies have demonstrated that signals from multiple RGC types converge onto thalamocortical (TC) neurons, even at the level of individual dendrites. The extent of which different RGC types participate in these synaptic triads and how inhibition shapes integration of information from the retina in the dLGN is poorly understood. Retinogeniculate triads ensure that excitation and inhibition arrive with high spatiotemporal precision onto dendritic appendages of TC neurons. The overall goal of this proposal is to understand the function of retinogeniculate triads in coordinating dendritic integration at the retinogeniculate synapse. Specifically, this study will address two aims: (1)To assess the functional organization of RGC types into retinogeniculate triads and (2) To determine how local feedforward inhibition transforms responses in TC dendrites. The proposed experiments involve high-resolution visualization of synaptic input organization along TC dendrites and manipulation of activity in presynaptic terminals to understand how incoming visual signals are integrated across dendritic compartments. In conducting these experiments, I will learn how to pair optogenetics/chemogenetics with physiological methods, including patch-clamp electrophysiology and calcium imaging. Additionally, I will receive extensive training in large-scale data analysis for experiments related to super-resolution microscopy, electron microscopy, and in vivo calcium imaging. This proposed research will provide unique training that will prepare me for an independent career in dendritic and sensoryintegration.

项目概要 大脑最显着的特性之一是它计算和整合信息的能力。在 视觉系统，视觉场景的处理从眼睛开始，下面的视网膜电路在眼睛中分离 信息进入 30 – 40 个不同的功能通道，每个通道编码一个特定的视觉特征。视网膜 神经节细胞（RGC）是视网膜的输出神经元，将这些信号传递到下游视觉中枢 它们被整合起来以调节感知和驱动行为。视网膜原突触位于 背外侧膝状核（dLGN）代表眼睛和大脑之间的第一个连接 已在多个物种中得到广泛研究。视网膜原突触的一个显着特征是 视网膜输入很容易组织成具有抑制性末端的突触三联体， 突触后树突创建一个用于快速前馈抑制的局部电路。最近的研究有 证明来自多种 RGC 类型的信号会汇聚到丘脑皮质 (TC) 神经元，即使在 单个树突的水平。不同 RGC 类型参与这些突触三联体的程度和 人们对抑制如何影响 dLGN 中视网膜信息的整合知之甚少。 Retinogeniculate 三联体确保兴奋和抑制以高时空精度到达 TC 神经元的树突附属物。该提案的总体目标是了解 视网膜原三联体在视网膜原突触处协调树突整合。具体来说，这 研究将解决两个目标：（1）评估 RGC 类型的功能组织为视网膜原化 (2) 确定局部前馈抑制如何改变 TC 树突的响应。这 提出的实验涉及沿 TC 树突的突触输入组织的高分辨率可视化 以及操纵突触前末梢的活动以了解传入的视觉信号是如何发生的 跨树突区室整合。 在进行这些实验时，我将学习如何将光遗传学/化学遗传学与生理学相结合 方法，包括膜片钳电生理学和钙成像。此外，我还将收到广泛的 超分辨率显微镜、电子相关实验的大规模数据分析培训 显微镜和体内钙成像。这项拟议的研究将提供独特的培训，为 我希望在树突和感觉统合方面有一个独立的职业生涯。