Dendritic integration at the retinogeniculate synapse

项目摘要 大脑最显著的特性之一是其计算和整合信息的能力。在 视觉系统，视觉场景的处理始于眼睛，在那里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 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的视觉中心 在那里，它们被整合在一起，以调节感知和驱动行为。视黄素原性突触在脑内的分布 背外侧膝状核(DLGN)是眼睛和大脑之间的第一个连接， 已经在多种物种中得到了广泛的研究。视黄素原性突触的一个显著特征是 视网膜输入有很高的倾向于组织成带有抑制性终末的突触三联体 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 证明了来自多种RGC类型的信号会聚到丘脑皮质(TC)神经元，即使在 单个树枝晶的水平。不同类型的RGC在这些突触三联体中的参与程度以及 抑制如何影响dLGN中视网膜信息的整合，目前还知之甚少。 视网膜再生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。本提案的总体目标是了解 视黄素生成三联体在协调视黄素生成突触的树突整合中的作用。具体地说，这 这项研究将达到两个目标：(1)评估RGC类型到视网膜原化的功能组织 确定局部前馈抑制如何改变TC树突中的反应。这个 所提出的实验涉及沿着TC树突的突触输入组织的高分辨率可视化 以及对突触前终端中的活动的操纵，以了解传入的视觉信号是如何 整合在树枝状的隔间。 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配对。 方法包括膜片钳电生理和钙离子成像。另外，我会收到大量的 培训与超分辨显微镜、电子技术相关的实验的大规模数据分析 显微镜和活体钙成像。这项拟议的研究将提供独特的培训，以准备 我希望在树突和感官整合方面有一个独立的职业生涯。

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.