Dendritic integration at the retinogeniculate synapse

视网膜原突触处的树突整合

• 批准号: 10389037
• 负责人: Hector Acaron
• 金额: $ 6.72万
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10389037
• 关键词: Address; Algorithms; Axon; Behavior; Biological Models; Brain; Calcium; Data Analyses; Dendrites; Dendrodendritic Synapse; Dorsal; Electron Microscopy; Electrophysiology (science); Ensure; Equilibrium; Exhibits; Eye; Functional Imaging; Goals; Guidelines; Histology; Image; Individual; Interneurons; Knowledge; Label; Lateral Geniculate Body; Learning; Light; Mediating; Methods; Microscopy; Mus; Nervous system structure; 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; Triad Acrylic Resin; Vertebral column; Visual; Visual evoked cortical potential; Visual system structure; Visualization; appendage; autism spectrum disorder; career; cell type; experimental study; in vivo; in vivo calcium imaging; insight; large scale data; neurotransmission; optogenetics; patch clamp; postsynaptic; presynaptic; relating to nervous system; response; retinal neuron; retinogeniculate; sensory integration; spatiotemporal; 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.

项目摘要 大脑最显著的特性之一是它计算和整合信息的能力。在 在视觉系统中，视觉场景的处理开始于眼睛，在眼睛中，潜在的视网膜回路分离 信息分成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 视网膜的输出神经元神经节细胞（RGCs）将这些信号传递到下游视觉中心 在那里它们被整合来调节感知和驱动行为。视网膜神经节的视网膜膝状体突触 背外侧膝状体核（dLGN）代表眼睛和大脑之间的第一个连接， 在多个物种中被广泛研究。视网膜膝状体突触的一个显著特征是， 视网膜输入具有组织成具有抑制性末端的突触三联体的高度倾向， 突触后树突形成快速前馈抑制的局部回路。最近的研究 表明，来自多种RGC类型的信号会聚到丘脑皮质（TC）神经元，即使在 单个树突的水平。不同类型的RGC参与这些突触三联体的程度， 对于抑制如何影响视网膜信息在dLGN中的整合，人们知之甚少。 视网膜膝状体三合会确保兴奋和抑制以高时空精度到达 TC神经元的树突状附属物。本提案的总体目标是了解 在协调视网膜膝状体突触处的树突整合中，视网膜膝状体三联体起作用。具体来说， 本研究的目的有两个：（1）研究视网膜神经节细胞（RGC）在视网膜膝状体（retinogeniculate）中的功能组织 （2）确定局部前馈抑制如何改变TC树突的反应。的 所提出的实验包括沿着TC树突的突触输入组织的高分辨率可视化 和操纵突触前末梢的活动，以了解传入的视觉信号是如何 整合在树突状区室中 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 方法，包括膜片钳电生理学和钙成像。此外，我还将收到大量 培训大规模数据分析实验相关的超分辨率显微镜，电子 显微镜和体内钙成像。这项拟议的研究将提供独特的培训， 我在树突和感觉集成方面的独立职业生涯。