MAPPING RETINOTECTAL CIRCUITS FOR VISUAL-EVOKED INNATE BEHAVIORS

绘制视觉诱发先天行为的视网膜环路

• 批准号: 10676764
• 负责人: Xin Duan
• 金额: $ 75.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676764
• 关键词: Anatomy; Animal Behavior; Area; Axon; Behavior; Behavioral; Binding; Bioinformatics; Brain; Communication; Complex; Data; Development; Electrophysiology (science); Engineering; Ensure; Freezing; Future; Genetic; Glycoproteins; Goals; Histology; Image; Individual; Instinct; Integrins; Knowledge; Label; Lead; Link; Maps; Measurement; Mediating; Methods; Midbrain structure; Molecular; Motion; Mus; Nervous System Physiology; Neurons; Output; Population; Resolution; Retina; Retinal Ganglion Cells; Role; Sorting; Specificity; Synapses; System; Tectum Mesencephali; Tracer; Visual; Visual System; Wheat Germ Agglutinins; Work; axon growth; defense response; empowerment; excitatory neuron; extracellular; ganglion cell; genetic analysis; genetic manipulation; inhibitory neuron; insight; nephronectin; neural circuit; neuronal circuitry; optogenetics; postsynaptic; postsynaptic neurons; retinotectal; sequencing platform; single-cell RNA sequencing; superior colliculus Corpora quadrigemina; tool; visual processing

PROJECT SUMMARY The precise assembly of neural circuits ensures accurate neurological function and behavior. For example, to communicate specific aspects of the visual world to the brain, retinal ganglion cells (RGCs) find and form synaptic contacts with specific postsynaptic partners out of the heterogeneous neuronal population of retino-recipient areas in the brain. One such area is the superior colliculus (SC), which receives direct retinal inputs and sends commands for direct innate behaviors such as escape or prey capture. What are the molecular determinants for selective RGC to SC neuron wiring? How are parallel retinotectal circuits sorted onto different SC laminae and neuronal relays? How are distinct retinotectal circuits linked to defined visual evoked behaviors? This proposed study aims to answer these questions in the mouse visual system. To accomplish this goal, first, we will map out parallel retinotectal circuits. We have established an integrated anterograde-tracing and sequencing platform, Trans-Seq, that defines the outputome of a genetically- defined RGC subtype. We applied Trans-Seq to all RGC subtypes globally, α-RGCs, and On-Off direction- selective-ganglion-cells and reconstructed their differential outputomes onto superficial superior-collicular (sSC) neuron subtypes. We propose to apply Trans-Seq to other major RGC subtypes representing different visual features. The proposed studies will determine retinotectal circuit convergence and divergence at neuron subtype resolution. Second, we aim to understand cellular and molecular mechanisms regulating specific retinotectal circuit wiring. We have analyzed α-RGC specific outputomes and revealed a selective sSC neuron subtype, Nephronectin-positive-wide-field neurons (NPWFs). The α-RGC-to-NPWF circuit was genetically validated using imaging, electrophysiology, and retrograde tracing. We propose to study how Nephronectin mediates α-RGC selective axonal lamination onto the deep sSC layer and whether Nephronectin determines the subsequent synaptic specificity from α-RGCs to NPWFs. We will also investigate what molecular mechanisms mediate Nephronectin binding and lead to a selective mammalian retinotectal circuit assembly. Third, we will link specific retinotectal circuits to defined visual evoked behaviors. We propose to combine genetic and optogenetic tools established above to determine whether the α-RGC-to-NPWF circuit contributes to visual evoked innate behaviors, such as looming triggered defense responses. We will also examine whether molecular determinants for connectivity, such as Nephronectin, regulate this behavioral output via these retinotectal circuits. Our circuit mapping platform builds a precise connectivity map at neuronal subtype resolution. Further, this work will align the precise neuronal wiring diagram to innate visual evoked behaviors, informing future functional and behavioral analysis. The new knowledge gained here may include molecular principles underlying mammalian circuit wiring relevant beyond the visual system.

项目概要 神经回路的精确组装保证了准确的神经功能和行为。 例如，为了将视觉世界的特定方面传达给大脑，视网膜神经节细胞 (RGC) 会发现并 与异质神经群体中的特定突触后伙伴形成突触接触 大脑中的视网膜接收区域之一是上丘（SC），它直接接收视网膜。 输入和发送命令以进行直接的先天行为，例如逃跑或捕获猎物。什么是分子。 选择性 RGC 到 SC 神经元连接的决定因素如何将并行视网膜顶盖电路分类到不同的位置？ SC 层和神经中继如何与定义的视觉诱发行为联系起来？ 这项研究旨在回答小鼠视觉系统中的这些问题。 为了实现这一目标，首先，我们将绘制出并行的视网膜顶盖电路。 集成的顺行追踪和测序平台 Trans-Seq，定义了基因组的输出组 我们将 Trans-Seq 应用于全局所有 RGC 亚型、α-RGC 和开关方向 - 选择性神经节细胞并将其差异输出组重建到浅表上丘脑（sSC）上 我们建议将 Trans-Seq 应用于代表不同视觉的其他主要 RGC 亚型。 拟议的研究将确定神经亚型的视网膜顶盖回路的收敛和发散。 其次，我们的目标是了解调节特定视网膜顶盖的细胞和分子机制。 我们分析了 α-RGC 特异性输出组并揭示了选择性 sSC 神经元亚型， 肾连蛋白阳性宽视野神经元 (NPWF) 使用 α-RGC 至 NPWF 电路进行了基因验证。 我们建议研究肾连接蛋白如何介导 α-RGC。 选择性轴突层压到深层 sSC 层以及肾连蛋白是否决定后续 我们还将研究从 α-RGC 到 NPWF 的突触特异性。 肾连接蛋白结合并导致选择性哺乳动物视网膜顶盖电路组装。第三，我们将连接特异性。 我们建议结合遗传和光遗传学工具来定义视觉诱发行为。 上面建立的以确定 α-RGC-to-NPWF 回路是否有助于视觉诱发先天 行为，例如迫在眉睫的触发防御反应，我们还将研究分子决定因素。 用于连接的神经连接蛋白（例如肾连接蛋白）通过这些视网膜顶盖电路调节这种行为输出。 我们的电路映射平台以神经亚型分辨率构建精确的连接图。 这项工作将把精确的神经接线图与先天的视觉诱发行为结合起来，为未来提供信息 这里获得的新知识可能包括分子基本原理。 哺乳动物的电路布线与视觉系统无关。

项目成果

Spatiotemporal molecular dynamics of the developing human thalamus.

发育中的人类丘脑的时空分子动力学。

• 发表时间: 2023-10-13
• 作者: Kim, Chang N;Shin, David;Wang, Albert;Nowakowski, Tomasz J
• 通讯作者: Nowakowski, Tomasz J

A cognitive process occurring during sleep is revealed by rapid eye movements.

睡眠期间发生的认知过程通过快速眼球运动来揭示。

• 发表时间: 2022-08-26
• 作者: Senzai, Yuta;Scanziani, Massimo
• 通讯作者: Scanziani, Massimo

A genetically defined tecto-thalamic pathway drives a system of superior-colliculus-dependent visual cortices.

基因定义的顶盖丘脑通路驱动依赖于上丘的视觉皮层系统。

• 发表时间: 2023-07-19
• 影响因子: 16.2
• 作者: Brenner, Joshua M;Beltramo, Riccardo;Gerfen, Charles R;Ruediger, Sarah;Scanziani, Massimo
• 通讯作者: Scanziani, Massimo