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Parallel Tectothalamic Pathways

平行的顶盖丘脑通路

基本信息

批准号：
9816337
负责人：
MARTHA E BICKFORD
金额：
$ 38.82万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-02 至 2022-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9816337
关键词：
Address Affect Animals Axon Behavior Behavior assessment Bilateral Birds Brain Brain region Cell Nucleus Cells Disease Dyslexia Electric Stimulation Electrodes Electrons Evaluation Freezing Frequencies Glutamates Goals Head Homologous Gene In Vitro Knowledge Link Mammals Measures Mediating Methods Microscopic Midbrain structure Motion Motion Perception Motor Movement Mus Neurons Output Pathway interactions Pattern Property Pulvinar structure Reaction Retina Retinal Running Schizophrenia Sensory Signal Transduction Slice Specificity Stimulus Synapses System Techniques Testing Thalamic structure Visual Visual Fields Visual Motion Visual Pathways Work autism spectrum disorder base behavioral response brain circuitry cell type design experimental study innovation optical fiber optogenetics photoactivation receptive field response superior colliculus Corpora quadrigemina visual motor visual stimulus

项目摘要

Summary/Abstract The proposed experiments are designed to examine how sensory selectivity is adjusted to initiate appropriate behavior. In mice, two fundamental visually-evoked behaviors, freezing and escape, are initiated respectively by the movement of a small disc that moves slowly across the visual field (sweeping), or a disc that rapidly expands to fill the visual field (looming). However, the synaptic interactions that mediate the selection of these visually-evoked responses are largely unknown. In the superior colliculus (SC), wide field vertical (WFV) cells respond to sweeping or looming stimuli and project to the thalamic pulvinar nucleus (PUL), a brain region involved in the initiation of visually-guided behavior. WFV cells receive input from the retina and V1, intrinsic SC neurons, and the parabigeminal nucleus (PBG). Based on previous studies of the avian nucleus isthmi (considered the PBG homologue), we hypothesize that SC-PBG connections gate the responses of WFV cells to their retinal input, and this stimulus selection network determines the subsequent initiation of appropriate behavioral responses. We propose to examine SC-PBG circuits in detail, and test whether manipulating their activity can shift the responsiveness of WFV cells, alter PUL responses to sweeping and looming stimuli, or impact the initiation of visually-evoked freezing and escape behavior. We will study this system at multiple levels, from the ultrastructure of synapses to behavioral assessments, using an array of innovative strategies to examine circuit function with cell type specificity. The specific goals of the proposed experiments are: to characterize the ultrastructure of synaptic input to WFV cells and synaptic connections that link the SC and PBG (Aim 1a), test how optogenetic activation of the synaptic connections between the SC and PBG affect the responsiveness of WFV and PBG cells (Aim 1b), determine whether PUL receptive field properties differ based on their unique responses to WFV cell input (Aim 2a), test whether PUL responses are altered by manipulating SC-PBG circuits (Aim 2b), and determine if chemogenetic manipulation of SC-PBG pathways affects visually-evoked freezing or escape responses (Aim 3). We believe that this integrated approach can address how sensory selectivity is adjusted to initiate appropriate behavior, while providing the precision of single cell circuit analysis.

摘要/摘要拟议的实验旨在检验如何调整感官选择性，以启动适当的行为。在小鼠身上，两种基本的视觉诱发行为--冻结和逃逸--分别被启动通过在视场中缓慢移动的小圆盘的运动(扫视)，或快速移动的圆盘展开以填充视野(隐约可见)。然而，调节这些神经元选择的突触相互作用视觉诱发的反应在很大程度上是未知的。在上丘(SC)，广野垂直(WFV)细胞对掠过或隐约可见的刺激作出反应，并投射到丘脑枕核(PUL)，这是一个大脑区域参与启动视觉引导行为的。WFV细胞接受来自视网膜和固有的V1的输入 SC神经元和延髓旁核(PBG)。基于前人对鸟类峡核的研究 (考虑PBG同源物)，我们假设SC-PBG连接启动了WFV细胞的反应它们的视网膜输入，而这个刺激选择网络决定了随后适当的启动行为反应。我们建议详细检查SC-PBG电路，并测试是否操纵它们的活动可以改变WFV细胞的反应性，改变PUL对扫荡和隐约可见的刺激的反应，或者影响视觉诱发的冻结和逃逸行为的启动。我们将从多个方面研究这一系统水平，从突触的超微结构到行为评估，使用一系列创新策略以细胞类型特异性检测电路功能。拟议实验的具体目标是： WFV细胞突触输入的超微结构以及连接SC和Sc的突触连接 PBG(Aim 1a)，测试SC和PBG之间的突触连接的光遗传激活如何影响 WFV和PBG细胞的反应性(目标1b)，决定脉冲感受野特性是否不同根据它们对WFV细胞输入的独特反应(目标2a)，测试PUL反应是否由操纵SC-PBG通路(目标2b)，并确定SC-PBG通路的化学发生操纵影响视觉诱发的冻结或逃逸反应(目标3)。我们相信，这一综合办法可以阐述如何调整感官选择性以启动适当的行为，同时提供单电池电路分析。